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Theophylline in the Treatment of Respiratory Disease

  • Chapter
Pharmacology and Therapeutics of Asthma and COPD

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 161))

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Abstract

Theophylline has now been in clinical use, most notably in the treatment of respiratory disease, for more than a century. Traditionally classified as a bronchodilator drug, it is becoming increasingly apparent that theophylline has a range of other pharmacological effects of potential therapeutic value in the treatment of respiratory diseases. Anti-inflammatory and immunomodulatory actions of theophylline have been observed both in the laboratory with respect to inflammatory cell function and in the clinic in patient populations suffering with a range of respiratory diseases. Many of the biological effects of theophylline have been suggested to occur via an inhibitory effect on the phosphodiesterase (PDE) family of enzymes; however, studies have also shown theophylline to antagonise adenosine receptors, inhibit NF-kB, a transcription factor important in regulation of inflammatory cell cytokine activity, inhibit interleukin (IL)-5 or granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced eosinophil survival, enhance histone deacetylase (HDAC) activity and affect lipid kinase and protein kinase activities in inflammatory cells. Research will no doubt continue in order to elucidate these mechanisms in an attempt to produce a theophylline-type drug with greater selectivity and higher therapeutic index, which in turn may lead to improved patient compliance and greater control of airway inflammation.

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References

  • Ali, S., Mustafa, S. J., and Metzger, W. J. Adenosine receptor-mediated bronchoconstriction and bronchial hyperresponsiveness in allergic rabbit model. Am.J.Physiol 266 (3 Pt 1), L271 - L277. 1994

    PubMed  CAS  Google Scholar 

  • Ashutosh, K., Sedat, M., and Fragale-Jackson, J. Effects of theophylline on respiratory drive in patients with chronic obstructive pulmonary disease. J.Clin.Pharmacol. 37 (12), 1100–1107. 1997

    PubMed  CAS  Google Scholar 

  • Aubier, M. Effect of theophylline on diaphragmatic and other skeletal muscle function. J Allergy Clin.Immunol. 78 (4 Pt 2), 787–792. 1986

    Article  PubMed  CAS  Google Scholar 

  • Aubier, M., Neukirch, C., Maachi, M., Boucara, D., Engelstatter, R., Steinijans, V., Samoyeau, R., and Dehoux, M. Effect of slow-release theophylline on nasal antigen challenge in subjects with allergic rhinitis. European Respiratory Journal 11 (5), 1105–1110. 1998

    Article  PubMed  CAS  Google Scholar 

  • Baker, A. J. and Fuller, R. W. Effect of cyclic adenosine monophosphate, 5’-(N- ethylcarboxyamido)-adenosine and methylxanthines on the release of thromboxane and lysosomal enzymes from human alveolar macrophages and peripheral blood monocytes in vitro. Eur.J.Pharmacol. 211 (2), 157–161. 1992

    Article  PubMed  CAS  Google Scholar 

  • Banner, K. H., Harbinson, P., Costello, J. F., and Page, C. P. Effect of PDE inhibitors on the proliferation of human peripheral blood mononuclear cells (HPBM) from mild asthmatics and normals. Am.J.Resp.Crit.Care Med. 155 (4). 1997a

    Google Scholar 

  • Banner, K. H., Hoult, J. R., Taylor, M. N., Landells, L. J., and Page, C. P. Possible Contribution of Prostaglandin E2 to the antiproliferative effect of phosphodiesterase 4 inhibitors in human mononuclear cells. Biochem.Pharmacol. 58(9), 1487–1495. 1–111999

    Google Scholar 

  • Banner, K. H. and Page, C. Prostaglandins contribute to the anti-proliferative effect of isoenzyme selective phosphodiesterase 4 inhibitors but not theophylline in human mononuclear cells. Br.J.Pharmacol. 120. 1997b

    Google Scholar 

  • Barnes, P. J. Managing Chronic Obstructive Pulmonary Disease. 2nd. 2000. Science Press Ltd

    Google Scholar 

  • Barnes, P. J. New concepts in chronic obstructive pulmonary disease. Annu.Rev.Med. 54, 113–129. 2003

    Article  PubMed  CAS  Google Scholar 

  • Barnes, P. J., Jonsson, B., and Klim, J. B. The costs of asthma. Eur.Respir.J. 9 (4), 636–642. 1996

    Article  PubMed  CAS  Google Scholar 

  • Barnes, P. J. and Pauwels, R. A. Theophylline in the management of asthma: time for reappraisal? Eur.Respir.J. 7 (3), 579–591. 1994

    Article  PubMed  CAS  Google Scholar 

  • Becker, A. B., Simons, K. J., Gillespie, C. A., and Simons, E E. The bronchodilator effects and pharmacokinetics of caffeine in asthma. N.Engl.J.Med. 310, 743–746. 1984

    Article  PubMed  CAS  Google Scholar 

  • Bel, E. H., Timmers, M. C., Zwinderman, A. H., Dijkman, J. H., and Sterk, P. J. The effect of inhaled corticosteroids on the maximal degree of airway narrowing to methacholine in asthmatic subjects. Am.Rev.Respir.Dis. 143 (1), 109–113. 1991a

    PubMed  CAS  Google Scholar 

  • Bel, E. H., Zwinderman, A. H., Timmers, M. C., Dijkman, J. H., and Sterk, P. J. The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease. Thorax 46 (1), 9–14. 1991b

    Article  PubMed  CAS  Google Scholar 

  • Bessler, H., Gilgal, R., Djaldetti, M., and Zahavi, I. Effect of pentoxifylline on the phagocytic activity, cAMP levels, and superoxide anion production by monocytes and polymorphonuclear cells. J.Leukoc.Biol. 40 (6), 747–754. 1986

    PubMed  CAS  Google Scholar 

  • Bjorck, T., Gustafsson, L. E., and Dahlen, S. E. Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine. Am.Rev.Respir.Dis. 145 (5), 1087–1091. 1992

    Article  PubMed  CAS  Google Scholar 

  • Bloemen, P. G., van-den-Tweel, M. C., Henricks, P. A., Engels, F., Kester, M. H., van-deLoo, P. G., Blomjous, F. J., and Nijkamp, E P. Increased cAMP levels in stimulated neutrophils inhibit their adhesion to human bronchial epithelial cells. Am.J.Physiol. 272 (4 Pt 1), L580 - L587. 1997

    PubMed  CAS  Google Scholar 

  • Brenner, M., Berkowitz, R., Marshall, N., and Strunk, R. C. Need for theophylline in severe steroid-requiring asthmatics. Clin.Allergy 18 (2), 143–150. 1988

    Article  PubMed  CAS  Google Scholar 

  • Buckley, J. T. Properties of human erythrocyte phosphatidylinositol kinase and inhibition by adenosine, ADP and related compounds. Biochim.Biophys.Acta 498(1), 1–9. 23–61977

    Google Scholar 

  • Carletto, A., Biasi, D., Bambara, L. M., Caramaschi, P., Bonazzi, M. L., Lussignoli, S., Andrioli, G., and Bellavite, R Studies of skin-window exudate human neutrophils: increased resistance to pentoxifylline of the respiratory burst in primed cells. Inflammation 21 (2), 191–203. 1997

    Article  PubMed  CAS  Google Scholar 

  • Chrystyn, H., Mulley, B. A., and Peake, M. D. Dose response relation to oral theophylline in severe chronic obstructive airways disease. BMJ 297(6662), 1506–1510. 10–121988

    Google Scholar 

  • Cockcroft, D. W., Murdock, K. Y., Gore, B. P., O’Byrne, R M., and Manning, P. Theophylline does not inhibit allergen-induced increase in airway responsiveness to methacholine. J.Allergy Clin.Immunol. 83 (5), 913–920. 1989

    Article  PubMed  CAS  Google Scholar 

  • Columbo, M., Horowitz, E. M., McKenzie, White, Kagey, Sobotka, and Lichtenstein, L. M. Pharmacologic control of histamine release from human basophils induced by platelet-activating factor. Int.Arch.Allergy Immunol. 102 (4), 383–390. 1993

    Article  PubMed  CAS  Google Scholar 

  • Cooper, C. B., Davidson, A. C., and Cameron, I. R. Aminophylline, respiratory muscle strength and exercise tolerance in chronic obstructive airway disease. Bull.Eur Physiopathol.Respir 23 (1), 15–22. 1987

    PubMed  CAS  Google Scholar 

  • Coward, W. R., Sagara, H., and Church, M. K. Asthma, adenosine, mast cells and theophylline. Clin.Exp.Allergy 28 Suppl 3, 42–46. 1998

    Google Scholar 

  • Cox, L. R., Murphy, S. K., and Ramos, K. Modulation of phosphoinositide metabolism in aortic smooth muscle cells by allylamine. Exp.Mol.Pathol. 53 (1), 52–63. 1990

    Article  PubMed  CAS  Google Scholar 

  • Crescioli, S., Spinazzi, A., Plebani, M., Pozzani, M., Mapp, C. E., Boschetto, P., and Fabbri, L. M. Theophylline inhibits early and late asthmatic reactions induced by allergens in asthmatic subjects. Ann.Allergy 66 (3), 245–251. 1991

    PubMed  CAS  Google Scholar 

  • Crocker, I. C., Townley, R. G., and Khan, M. M. Phosphodiesterase inhibitors suppress proliferation of peripheral blood mononuclear cells and interleukin-4 and -5 secretion by human T-helper type 2 cells. Immunopharmacology 31, 223–235. 1996

    Article  PubMed  CAS  Google Scholar 

  • Culpitt, S. V., de Matos, C., Russell, R. E., Donnelly, L. E., Rogers, D. F., and Barnes, R J. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease. Am.J Respir Crit Care Med. 165(10), 1371–1376. 15–5–2002

    Google Scholar 

  • Cushley, M. J., Tattersfield, A. E., and Holgate, S. T. Inhaled adenosine and guanosine on airway resistance in normal and asthmatic subjects. Br.J.Clin.Pharmacol. 15 (2), 161–165. 1983

    Article  PubMed  CAS  Google Scholar 

  • Cushley, M. J., Tattersfield, A. E., and Holgate, S. T. Adenosine-induced bronchoconstriction in asthma Antagonism by inhaled theophylline. Am.Rev.Respir.Dis. 129 (3), 380–384. 1984

    PubMed  CAS  Google Scholar 

  • D’Alonzo, G. E., Smolensky, M. H., Feldman, S, Gianotti, L. A., Emerson, M. B., Staudinger, H., and Steinijans, V. W. Twenty-four hour lung function in adult patients with asthma. Chronoptimized theophylline therapy once-daily dosing in the evening versus conventional twice-daily dosing. Am.Rev.Respir.Dis. 142 (1), 84–90. 1990

    PubMed  Google Scholar 

  • Darnall-Jr, R. A. Aminophylline reduces hypoxic ventilatory depression: possible role of adenosine. Pediatr.Res. 19 (7), 706–710. 1995

    Google Scholar 

  • De Monchy, J. G., Kauffman, H. E, Venge, R, Koeter, G. H., Jansen, H. M., Sluiter, H. J., and de Vries, K. Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. Am.Rev.Respir.Dis. 131 (3), 373–376. 1985

    PubMed  Google Scholar 

  • Derian, C. K., Santulli, R. J., Rao, R E., Solomon, H. E, and Barrett, J. A. Inhibition of chemotactic peptide-induced neutrophil adhesion to vascular endothelium by cAMP modulators. J.Immunol. 154 (1), 308–317. 1995

    PubMed  CAS  Google Scholar 

  • Di Stefano, A., Caramori, G., Oates, T., Capelli, A., Lusuardi, M., Gnemmi, I., Ioli, F., Chung, K. F., Donner, C. F., Barnes, P. J., and Adcock, I. M. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD. Eur Respir J 20 (3), 556–563. 2002

    Article  PubMed  CAS  Google Scholar 

  • Dullinger, D., Kronenberg, R., and Niewoehner, D. E. Efficacy of inhaled metaproterenol and orally-administered theophylline in patients with chronic airflow obstruction. Chest 89(2), 171–173. 1986 el

    Google Scholar 

  • Hashim, A., D’Agostino, B., Matera, M. G., and Page, C. Characterization of adenosine receptors involved in adenosine-induced bronchoconstriction in allergic rabbits. Br.J.Pharmacol. 119 (6), 1262–1268. 1996

    Article  PubMed  Google Scholar 

  • Elferink, J. G., Huizinga, T. W., and de–Koster, B. M. The effect of pentoxifylline on human neutrophil migration: a possible role for cyclic nucleotides. Biochem.Pharmacol. 54(4), 475–480. 15–8–1997

    Google Scholar 

  • Elliott, K. R. and Leonard, E. J. Interactions of formylmethionyl-leucyl-phenylalanine, adenosine, and phosphodiesterase inhibitors in human monocytes. Effects on superoxide release, inositol phosphates and cAMP. FEBS Lett. 254 (1–2), 94–98. 1989

    Article  PubMed  CAS  Google Scholar 

  • Endres, S., Fulle, H. J., Sinha, B., Stoll, D., Dinarello, C. A., Gerzer, R., and Weber, P. C. Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells. Immunology 72 (1), 56–60. 1991

    PubMed  CAS  Google Scholar 

  • Enk, A. H., Angeloni, V. L., Udey, M. C., and Katz, S. I. Inhibition of Langerhans cell antigen–presenting function by IL–10. A role for IL–10 in induction of tolerance. J.Immunol. 151(5), 2390–2398. 1–9–1993

    Google Scholar 

  • Evans, D. J., Taylor, D. A., Zetterstrom, O., Chung, K. F., O’Connor, B. J., and Barnes, P. J. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N.Engl.J.Med 337, 1412–1418. 1997

    Article  PubMed  CAS  Google Scholar 

  • Ezeamuzie, C. I. Involvement of A(3) receptors in the potentiation by adenosine of the inhibitory effect of theophylline on human eosinophil degranulation: possible novel mechanism of the anti–inflammatory action of theophylline. Biochem.Pharmacol. 61(12),1551–1559.15–6–2001

    Google Scholar 

  • Feoktistov, I and Biaggioni, I. Adenosine Alb receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. J.Clin.Invest. 96 (4), 1979–1986. 1995

    Google Scholar 

  • Feoktistov, I., Polosa, R., Holgate, S. T., and Biaggioni, I. Adenosine A2B receptors: a novel therapeutic target in asthma? Trends Pharmacol.Sci. 19 (4), 148–153. 1998

    Article  PubMed  CAS  Google Scholar 

  • Ferrer, P., Dihn-Xuan, T., and Chanal, I. Bronchodilator activity of LAS 31025, a new selective phosphodiesterase inhibitor. Am.J Respir Crit Care Med. 155. 1997

    Google Scholar 

  • Ferretti, M. E., Spisani, S., Pareschi, M. C., Buzzi, M., Cavallaro, R., Traniello, S., Reali, E., Torrini, I, Paradisi, M. P., and Zecchini, G. P. Two new formulated peptides able to activate chemotaxis and respiratory burst selectively as tools for studying human neutrophil responses. Cell Signal. 6 (1), 91–101. 1994

    Article  PubMed  CAS  Google Scholar 

  • Fink, G., Mittelman, M., Shohat, B., and Spitzer, S. A. Theophylline-induced alterations in cellular immunity in asthmatic patients. Clin.Allergy 17 (4), 313–316. 1987

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein, R., Fraser, R. S., and Ghezzo, H. Alveolar inflammation and its relation to emphysema in smokers. Am.J.Resp.Crit.Care Med. 152, 1666–1672. 1995

    PubMed  CAS  Google Scholar 

  • Finnerty, J. P., Lee, C., Wilson, S., Madden, J., Djukanovic, R., and Holgate, S. T. Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects: a placebo-controlled parallel group study. Eur.Respir.J. 9, 1672–1677. 1996

    Article  PubMed  CAS  Google Scholar 

  • Fonteh, A. N., Winkler, J. D., Torphy, T. J., Heravi, J., Undem, B. J., and Chilton, F. H. Influence of isoproterenol and phosphodiesterase inhibitors on platelet-activating factor biosynthesis in the human neutrophil. J.Immunol. 151 (1), 339–350. 1993

    PubMed  CAS  Google Scholar 

  • Foukas, L. C., Daniele, N., Ktori, C., Anderson, K. E., Jensen, J., and Shepherd, P. R. Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3–kinases. Differential effects on lipid kinase and protein kinase activities. J Biol.Chem. 277(40), 37124–37130. 4–10–2002

    Google Scholar 

  • Franzini, E., Sellak, H., Babin, Chevaye C., Hakim, J., and Pasquier, C. Effects of pentoxifylline on the adherence of polymorphonuclear neutrophils to oxidant-stimulated human endothelial cells: involvement of cyclic AMP. J.Cardiovasc.Pharmacol. 25 Suppl 2, S92 - S95. 1995

    Google Scholar 

  • Frossard, N., Landry, Y., Pauli, G., and Ruckstuhl, M. Effects of cyclic AMP- and cyclic GMP- phosphodiesterase inhibitors on immunological release of histamine and on lung contraction. Br.J.Pharmacol. 73 (4), 933–938. 1981

    Article  PubMed  CAS  Google Scholar 

  • Gardette, J., Margelin, D., Maziere, J. C., Bertrand, J., and Picard, J. Effect of dibutyryl cyclic AMP and theophylline on lipoprotein lipase secretion by human monocyte-derived macrophages. FEBS Lett. 225 (1–2), 178–182. 1987

    Article  PubMed  CAS  Google Scholar 

  • Giembycz, M. A. Phosphodiesterase 4 inhibitors and the treatment of asthma: where are we now and where do we go from here? Drugs 59 (2), 193–212. 2000

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez, M. C., Diaz, P., Galleguillos, E R., Ancic, P., Cromwell, O., and Kay, A. B. Allergen-induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) T-cells in asthma. Relative increases in OKT8 cells in single early responders compared with those in late-phase responders. Am.Rev.Respir.Dis. 136 (3), 600–604. 1987

    Article  PubMed  CAS  Google Scholar 

  • Griswold, D. E., Webb, E. F., Breton, J., White, J. R., Marshall, P. J., and Torphy, T. J. Effect of selective phosphodiesterase type IV inhibitor, rolipram, on fluid and cellular phases of inflammatory response. Inflammation 17 (3), 333–344. 1993

    Article  PubMed  CAS  Google Scholar 

  • Guillou, P. J., Ramsden, C., Kerr, M., Davison, A. M., and Giles, G. R. A prospective controlled clinical trial of aminophylline as an adjunctive immunosuppressive agent. Transplant.Proc. 16 (5), 1218–1220. 1984

    PubMed  CAS  Google Scholar 

  • Guyatt, G. H., Townsend, M., Pugsley, S. O., Keller, J. L., Short, H. D., Taylor, D. W., and Newhouse, M. T. Bronchodilators in chronic air-flow limitation. Effects on airway function, exercise capacity, and quality of life. Am.Rev.Respir Dis. 135 (5), 1069–1074. 1987

    PubMed  CAS  Google Scholar 

  • Hamid, Q., Azzawi, M., Ying, S., Moqbel, R., Wardlaw, A. J., Corrigan, C. J., Bradley, B., Durham, S. R., Collins, J. V., Jeffery, P. K., and. Expression of mRNA for interleukin5 in mucosal bronchial biopsies from asthma. J.Clin.Invest 87 (5), 1541–1546. 1991

    Article  PubMed  CAS  Google Scholar 

  • Hancock, W. W., Pleau, M. E., and Kobzik, L. Recombinant granulocyte-macrophage colony-stimulating factor down-regulates expression of IL-2 receptor on human mononuclear phagocytes by induction of prostaglandin E. J.Immunol. 140 (9), 3021–3025. 1988

    CAS  Google Scholar 

  • Hart, L. A., Krishnan, V. L., Adcock, I. M., Barnes, P. J., and Chung, K. F. Activation and localization of transcription factor, nuclear factor-kappaB, in asthma. Am.J Respir Crit Care Med. 158 (5 Pt 1), 1585–1592. 1998

    PubMed  CAS  Google Scholar 

  • Harvath, L., Robbins, J. D., Russell, A. A., and Seamon, K. B. cAMP and human neutro-phil chemotaxis. Elevation of cAMP differentially affects chemotactic responsiveness. J Immunol. 146 (1), 224–232. 1991

    PubMed  CAS  Google Scholar 

  • Hatzelmann, A., Tenor, H., and Schudt, C. Differential effects of non-selective and selective phosphodiesterase inhibitors on human eosinophil functions. Br.J.Pharmacol. 114 (4), 821–831. 1995

    Article  PubMed  CAS  Google Scholar 

  • Hay, J. G., Stone, P., Carter, J., Church, S., Eyre-Brook, A., Pearson, M. G., Woodcock, A. A., and Calverley, P. M. Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease. Eur Respir J 5 (6), 659–664. 1992

    PubMed  CAS  Google Scholar 

  • Hendeles, L., Harman, E., Huang, D., O’Brien, R., Blake, K., and Delafuente, J. Theophylline attenuation of airway responses to allergen: comparison with cromolyn metered-dose inhaler. J.Allergy Clin.Immunol. 95 (2), 505–514. 1995

    Article  PubMed  CAS  Google Scholar 

  • Hichami, A., Boichot, E., Germain, N., Legrand, A., Moodley, I, and Lagente, V. Involvement of cyclic AMP in the effects of phosphodiesterase IV inhibitors on arachidonate release from mononuclear cells. Eur.J.Pharmacol. 291 (2), 91–97. 1995

    Article  PubMed  CAS  Google Scholar 

  • Hidi, R., Timmermans, S., Liu, E., Schudt, C., Dent, G., Holgate, S. T., and Djukanovic, R. Phosphodiesterase and cyclic adenosine monophosphate-dependent inhibition of T-lymphocyte chemotaxis. Eur Respir J 15 (2), 342–349. 2000

    Article  PubMed  CAS  Google Scholar 

  • Honeyman, T. W., Strohsnitter, W., Scheid, C. R., and Schimmel, R. J. Phosphatidic acid and phosphatidylinositol labelling in adipose tissue. Relationship to the metabolic effects of insulin and insulin–like agents. Biochem.J 212(2), 489–498. 15–5–1983

    Google Scholar 

  • Hossain, M., Okubo, Y., and Sekiguchi, M. Effects of various drugs (staurosporine, herbimycin A, ketotifen, theophylline, FK506 and cyclosporin A) on eosinophil viability. Arerugi. 43 (6), 711–717. 1994

    PubMed  CAS  Google Scholar 

  • Imhof, A. and Wolfe, A. P. Transcription: gene control by targeted histone acetylation. Curr.Biol. 8(12), R422–R424. 4–6–1998

    Google Scholar 

  • Ito, K. and Adcock, I. M. Histone acetylation and histone deacetylation. Mol.Biotechnol. 20 (1), 99–106. 2002a

    Article  PubMed  CAS  Google Scholar 

  • Ito, K., Barnes, P. J., and Adcock, I. M. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-lbeta-induced histone H4 acetylation on lysines 8 and 12. Mol.Cell Biol. 20 (18), 6891–6903. 2000

    Article  PubMed  CAS  Google Scholar 

  • Ito, K., Lim, S., Caramori, G., Chung, K. E, Barnes, P. J., and Adcock, I. M. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J 15(6), 11101112. 2001

    Google Scholar 

  • Ito, K., Lim, S., Caramori, G., Cosio, B., Chung, K. F., Adcock, I. M., and Barnes, P. J. A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc.Natl.Acad.Sci.U.S.A 99(13), 8921–8926. 25–6–2002b

    Google Scholar 

  • Jaffar, Z. H., Sullivan, P., Page, C. P., and Costello, J. Low-dose theophylline modulates T-lymphocyte activation in allergen-challenged asthmatics. Eur.Respir.J. 9, 456–462. 1996

    Article  PubMed  CAS  Google Scholar 

  • Jarjour, N. N., Lacouture, P. G., and Busse, W. W. Theophylline inhibits the late asthmatic response to nighttime antigen challenge in patients with mild atopic asthma. Ann.Allergy Asthma Immunol. 81 (3), 231–236. 1998

    Article  PubMed  CAS  Google Scholar 

  • Javaheri, S. and Guerra, L. Lung function, hypoxic and hypercapnic ventilatory responses, and respiratory muscle strength in normal subjects taking oral theophylline. Thorax 45 (10), 743–747. 1990

    Article  PubMed  CAS  Google Scholar 

  • Jeurgens, U. R., Overlack, A., and Vetter, H. Theophylline inhibits the formation of leukotriene B4 (LTB4) by enhancement of cyclic-AMP and prostaglandin E2 (PGE2) production in normal human monocytes in vitro. Eur.Resp.J. 17S, 36–85. 1993

    Google Scholar 

  • Jones, N. A., Page, C., and Lever, R. The effect of selective phosphodiesterase (PDE) isoenzyme inhibition on F-MET-LEU-PHE (fMLP) and tumor necrosis factor-alpha induced human neutrophil elastase release. Am.J.Resp.Crit.Care Med. 163. 2001

    Google Scholar 

  • Kammer, G. M. The adenylate cyclase-cAMP-protein kinase A pathway and regulation of the immune response. Immunol.Today 9 (7–8), 222–229. 1988

    Article  PubMed  CAS  Google Scholar 

  • Kassis, S., Lee, J. C., and Hanna, N. Effects of prostaglandins and cAMP levels on monocyte IL-1 production. Agents Actions 27 (3–4), 274–276. 1989

    Article  PubMed  CAS  Google Scholar 

  • Keatings, V. M., Collins, P. D., and Scott, D. M. Differences in interleukin-8 and tumour necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am.J.Resp.Crit.Care Med. 153, 530–534. 1996

    PubMed  CAS  Google Scholar 

  • Kelloway, J. S., Wyatt, R. A., and Adlis, S. A. Comparison of patients’ compliance with prescribed oral and inhaled asthma medications. Arch.Intern.Med. 154(12), 13491352.27–6–1994

    Google Scholar 

  • Kidney, J., Dominguez, M., Taylor, P. M., Rose, M., Chung, K. F., and Barnes, P. J. Immunomodulation by theophylline in asthma. Demonstration by withdrawal of therapy. American Journal of Respiratory and Critical Care Medicine 151 (6), 1907–1914. 1995

    PubMed  CAS  Google Scholar 

  • Kita, H., Abu, Ghazaleh, Gleich, G. J., and Abraham, R. T. Regulation of Ig-induced eosinophil degranulation by adenosine 3’,5’-cyclic monophosphate. J.Immunol. 146 (8), 2712–2718. 1991

    PubMed  CAS  Google Scholar 

  • Knudsen, P. J., Dinarello, C. A., and Strom, T. B. Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J.Immunol. 137 (10), 3189–3194. 1986

    PubMed  CAS  Google Scholar 

  • Kongragunta, V. R., Druz, W. S., and Sharp, J. T. Dyspnea and diaphragmatic fatigue in patients with chronic obstructive pulmonary disease. Responses to theophylline. Am.Rev.Respir Dis. 137 (3), 662–667. 1988

    PubMed  CAS  Google Scholar 

  • Kosmas, E. N., Michaelides, S. A., Polychronaki, A., Roussou, T., Toukmatzi, S., Polychronopoulos, V., and Baxevanis, C. N. Theophylline induces a reduction in circulating interleukin-4 and interleukin-5 in atopic asthmatics [In Process Citation]. Eur Respir J 13 (1), 53–58. 1999

    PubMed  CAS  Google Scholar 

  • Kotecha, S., Taylor, I. K., and Shaw, R. J. Pharmacological modulation of platelet-derived growth factor (B) mRNA expression in alveolar macrophages and adherent monocytes. Pulm.Pharmacol. 7 (6), 383–391. 1994

    Article  PubMed  CAS  Google Scholar 

  • Kraft, M., Pak, J., Borish, L., and Martin, R. J. Theophylline’s effect on neutrophil function and the late asthmatic response. Journal of Allergy Clinical Immunology 98 (2), 251–257. 1996a

    Article  CAS  Google Scholar 

  • Kraft, M., Torvik, J. A., Trudeau, J. B., Wenzel, S. E., and Martin, R. J. Theophylline: potential antiinflammatory effects in nocturnal asthma. J.Allergy C1in.Immunol. 97 (6), 1242–1246. 1996b

    Article  CAS  Google Scholar 

  • Landells, L. J., Jensen, M. W., Orr, L. M., Spina, D., O’Connor, B. J., and Page, C. P. The role of adenosine receptors in the action of theophylline on human peripheral blood mononuclear cells from healthy and asthmatic subjects. Br.J.Pharmacol. 129 (6), 1140–1144. 2000a

    Article  PubMed  CAS  Google Scholar 

  • Landells, L. J., Spina, D., Souness, J. E., O’Connor, B. J., and Page, C. P. A biochemical and functional assessment of monocyte phosphodiesterase activity in healthy and asthmatic subjects. Pulm.Pharmacol.Ther. 13 (5), 231–239. 2000b

    Article  PubMed  CAS  Google Scholar 

  • Landsberg, K. F., Vaughan, L. M., and Heffner, J. E. The effect of theophylline on respiratory muscle contractility and fatigue. Pharmacotherapy 10 (4), 271–279. 1990

    PubMed  CAS  Google Scholar 

  • Lappin, D., Riches, D. W., Damerau, B., and Whaley, K. Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes. Biochem.J. 222 (2), 477–486. 1984

    PubMed  CAS  Google Scholar 

  • Lichtenstein, L. M. and Margolis, S. Histamine release in vitro: inhibition by catecholamines and methylxanthines. Science 161 (844), 902–903. 1968

    Article  PubMed  CAS  Google Scholar 

  • Lidington, E., Nohammer, C., Dominguez, M., Ferry, B., and Rose, M. L. Inhibition of the transendothelial migration of human lymphocytes but not monocytes by phosphodiesterase inhibitors. Clinical and Experimental Immunology 104, 66–71. 1996

    Article  PubMed  CAS  Google Scholar 

  • Lim, L. K., Hunt, N. H., and Weidemann, M. J. Reactive oxygen production, arachidonate metabolism and cyclic AMP in macrophages. Biochem.Biophys.Res.Commun. 114 (2), 549–555. 1983

    Article  PubMed  CAS  Google Scholar 

  • Lim, S., Tornita, K., Carramori, G., Jatakanon, A., Oliver, B., Keller, A., Adcock, I., Chung, K. F., and Barnes, P. J. Low–dose theophylline reduces eosinophilic inflammation but not exhaled nitric oxide in mild asthma. Am.J Respir Crit Care Med. 164(2), 273–276. 15–7–2001

    Google Scholar 

  • Limatibul, S., Shore, A., Dosch, H. M., and Gelfand, E. W. Theophylline modulation of E-rosette formation: an indicator of T-cell maturation. Clinical and Experimental Immunology 33 (3), 503–513. 1978

    PubMed  CAS  Google Scholar 

  • Lorenz, J. J., Furdon, P. J., Taylor, J. D., Verghese, M. W., Chandra, G., Kost, T. A., Haneline, S. A., Roner, L. A., and Gray, J. G. A cyclic adenosine 3’,5’-monophosphate signal is required for the induction of IL-1 beta by TNF-alpha in human monocytes. J.Immunol. 155 (2), 836–844. 1995

    PubMed  CAS  Google Scholar 

  • Louis, R., Bury, T., Corhay, J. L., and Radermecker, M. LY 186655, a phosphodiesterase inhibitor, inhibits histamine release from human basophils, lung and skin fragments. Int.J.Immunopharmacol. 14 (2), 191–194. 1992

    Article  PubMed  CAS  Google Scholar 

  • Louis, R. E. and Radermecker, M. F. Substance P-induced histamine release from human basophils, skin and lung fragments: effect of nedocromil sodium and theophylline. Int.Arch.Allergy Appl.Immunol. 92 (4), 329–333. 1990

    Article  PubMed  CAS  Google Scholar 

  • Magnussen, H., Reuss, G., and Jones, R. Theophylline has a dose-related effect on the airway response to inhaled histamine and methacholine in asthmatics. Am.Rev.Respir.Dis. 136 (5), 1163–1167. 1987

    Article  PubMed  CAS  Google Scholar 

  • Mahler, D. A., Matthay, R. A., Snyder, P. E., Wells, C. K., and Loke, J. Sustained-release theophylline reduces dyspnea in nonreversible obstructive airway disease. Am.Rev.Respir Dis. 131 (1), 22–25. 1985

    PubMed  CAS  Google Scholar 

  • Mann, J. S. and Holgate, S. T. Specific antagonism of adenosine-induced bronchoconstriction in asthma by oral theophylline. Br.J.Clin.Pharmacol. 19 (5), 685–692. 1985

    Article  PubMed  CAS  Google Scholar 

  • Mapp, C., Boschetto, P., dal Vecchio, L., Crescioli, S., de Marzo, N., Paleari, D., and Fabbri, L. M. Protective effect of antiasthma drugs on late asthmatic reactions and increased airway responsiveness induced by toluene diisocyanate in sensitized subjects. Am.-Rev Respir.Dis. 136 (6), 1403–1407. 1987

    Article  PubMed  CAS  Google Scholar 

  • Marsh, G. D., McFadden, R. G., Nicholson, R. L., Leasa, D. J., and Thompson, R. T. Theophylline delays skeletal muscle fatigue during progressive exercise. Am.Rev.Respir Dis. 147 (4), 876–879. 1993

    PubMed  CAS  Google Scholar 

  • Marvin, P. M., Baker, B. J., Dutt, A. K., Murphy, M. L., and Bone, R. C. Physiologic effects of oral bronchodilators during rest and exercise in chronic obstructive pulmonary disease. Chest 84 (6), 684–689. 1983

    Article  PubMed  CAS  Google Scholar 

  • Mary, D., Aussel, C., Ferrua, B., and Fehlmann, M. Regulation of interleukin 2 synthesis by cAMP in human T cells. J.Immunol. 139 (4), 1179–1184. 1987

    PubMed  CAS  Google Scholar 

  • Mascali, J. J., Cvietusa, P., Negri, J., and Borish, L. Anti-inflammatory effects of theophylline: modulation of cytokine production. Ann.Allergy Asthma Immunol. 77 (1), 3438. 1996

    Google Scholar 

  • Momose, T., Okubo, Y., Horie, S., Suzuki, J., Isobe, M., and Sekiguchi, M. Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression. International Archives of Allergy Immunology 117 (2), 138–145. 1998

    Article  CAS  Google Scholar 

  • Murciano, D., Aubier, M., Lecocguic, Y., and Pariente, R. Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease. N.Engl.J Med. 311(6), 349–353. 9–8–1984

    Google Scholar 

  • Murciano, D., Auclair, M. H., Pariente, R., and Aubier, M. A randomized, controlled trial of theophylline in patients with severe chronic obstructive pulmonary disease. N.Engl.J Med. 320(23), 1521–1525.8–6–1989

    Google Scholar 

  • Mygind, N. Glucocorticosteroids and rhinitis. Allergy 48 (7), 476–490. 1993

    Article  PubMed  CAS  Google Scholar 

  • Naclerio, R. M., Bartenfelder, D., Proud, D., Togias, A. G., Meyers, D. A., Kagey, Sobotka, Norman, P. S., and Lichtenstein, L. M. Theophylline reduces histamine release during pollen-induced rhinitis. J.Allergy Clin.Immunol. 78 (5 Pt 1), 874–876. 1986

    Article  PubMed  CAS  Google Scholar 

  • Nielson, C. P., Crowley, J. J., Cusack, B. J., and Vestal, R. E. Therapeutic concentrations of theophylline and enprofylline potentiate catecholamine effects and inhibit leukocyte activation. J.Allergy Clin.Immunol. 78 (4 Pt 1), 660–667. 1986

    Article  PubMed  CAS  Google Scholar 

  • Nielson, C. P., Crowley, J. J., Morgan, M. E., and Vestal, R. E. Polymorphonuclear leukocyte inhibition by therapeutic concentrations of theophylline is mediated by cyclic3’,5’-adenosine monophosphate. Am.Rev.Respir.Dis. 137 (1), 25–30. 1988

    Article  PubMed  CAS  Google Scholar 

  • Niwa, M., Hara, A., Kanamori, Y., Matsuno, H., Kozawa, O., Yoshimi, N., Mori, H., and Uematsu, T. Inhibition of tumor necrosis factor–alpha induced neutrophil apoptosis by cyclic AMP: involvement of caspase cascade. Eur.J.Pharmacol. 371(1), 59–67.23–4–1999

    Google Scholar 

  • Nourshargh, S. and Hoult, J. R. Inhibition of human neutrophil degranulation by forskolin in the presence of phosphodiesterase inhibitors. Eur.J.Pharmacol. 122 (2), 205–212. 1986

    Article  PubMed  CAS  Google Scholar 

  • Nyce, J. W. and Metzger, W. J. DNA antisense therapy for asthma in an animal model. Nature 385(6618), 721–725. 20–2–1997

    Google Scholar 

  • Ohta, K. and Yamashita, N. Apoptosis of eosinophils and lymphocytes in allergic inflammation. J Allergy Clin Immunol 104 (1), 14–21. 1999

    Article  PubMed  CAS  Google Scholar 

  • Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W., Meek, S. E., Salpekar, A., Waterfield, M. D., Smith, A. J., and Vanhaesebroeck, B. Impaired B and T cell antigen receptor signaling in p110delta PI 3– kinase mutant mice. Science 297(5583), 1031–1034. 9–8–2002

    Google Scholar 

  • Okubo, S., Konno, K., Ishizaki, T., Kubo, M., Suganuma, T., and Takizawa, T. Effect of theophylline on respiratory neuromuscular drive. Eur J Clin.Pharmacol. 33 (1), 85–88. 1987

    Article  PubMed  CAS  Google Scholar 

  • Orange, R. P., Kaliner, M. A., Laraia, P. J., and Austen, K. F. Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. II. Influence of cellular levels of cyclic AMP. Fed.Proc. 30 (6), 1725–1729. 1971

    PubMed  CAS  Google Scholar 

  • Ottonello, L., Gonella, R., Dapino, P., Sacchetti, C., and Dallegri, E Prostaglandin E2 inhibits apoptosis in human neutrophilic polymorphonuclear leukocytes: role of intracellular cyclic AMP levels. Exp.Hematol. 26 (9), 895–902. 1998

    CAS  Google Scholar 

  • Page, C. P., Cotter, T., Kilfeather, S., Sullivan, P., Spina, D., and Costello, J. F. Effect of chronic theophylline treatment on the methacholine dose-response curve in allergic asthmatic subjects. European Respiratory Journal 12 (1), 24–29. 1998

    Article  PubMed  CAS  Google Scholar 

  • Pardi, R., Zocchi, M. R., Ferrero, E., Ciboddo, G. E, Inverardi, L., and Rugarli, C. In vivo effects of a single infusion of theophylline on human peripheral blood lymphocytes. Clinical and Experimental Immunology 57(3), 722–728. 1984

    Google Scholar 

  • Paul, Eugene, Pene, J., Bousquet, J., and Dugas, B. Role of cyclic nucleotides and nitric oxide in blood mononuclear cell IgE production stimulated by IL-4. Cytokine 7 (1), 64–69. 1995

    Article  Google Scholar 

  • Pauwels, R., van Renterghem, D., van der Straeten, M., Johannesson, N., and Persson, C. G. The effect of theophylline and enprofylline on allergen-induced bronchoconstriction. J.Allergy Clin.Immunol. 76 (4), 583–590. 1985

    Article  PubMed  CAS  Google Scholar 

  • Peachell, P. T., MacGlashan, D. W., Jr., Lichtenstein, L. M., and Schleimer, R. P. Regulation of human basophil and lung mast cell function by cyclic adenosine monophosphate. J.Immunol. 140 (2), 571–579. 1988

    PubMed  CAS  Google Scholar 

  • Peachell, P. T., Undem, B. J., Schleimer, R. P., MacGlashan, D. W., Jr., Lichtenstein, L. M., Cieslinski, L. B., and Torphy, T. J. Preliminary identification and role of phosphodies-terase isozymes in human basophils. J.Immunol. 148 (8), 2503–2510. 1992

    PubMed  CAS  Google Scholar 

  • Pearce, F. L., Befus, A. D., Gauldie, J., and Bienenstock, J. Mucosal mast cells. II. Effects of anti-allergic compounds on histamine secretion by isolated intestinal mast cells. J.Immunol. 128 (6), 2481–2486. 1982

    Google Scholar 

  • Persson, C. G. and Pauwels, R. Pharmacology of Anti-Asthma Xanthines. (7), 207–225. 1989. Academic Press London.

    Google Scholar 

  • Pharmacology of Asthma. Page, C. and Barnes, P. J Persson, C. G. A. and Pauwels, R. Pharmacology of anti-asthma xanthines. Page, C. P. and Barnes, P. J. Pharmacology of asthma. (7), 207–225. 1991. Berlin, Springer-Verlag.

    Google Scholar 

  • Handbook of Experimental Pharmacology. Born, G. V. R., Cuatrecasas, P., and Her-ken, H Peterson, T. C., Slysz, G., and Isbrucker, R. The inhibitory effect of ursodeoxycholic acid and pentoxifylline on platelet derived growth factor-stimulated proliferation is distinct from an effect by cyclic AMP. Immunopharmacology 39 (3), 181–191. 1998

    Article  Google Scholar 

  • Platzer, C., Meisel, C., Vogt, K., Platzer, M., and Volk, H. D. Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int.Immunol. 7 (4), 517–523. 1995

    Article  PubMed  CAS  Google Scholar 

  • Punnonen, J., Punnonen, K., Jansen, C. T., and Kalimo, K. Interferon (IFN)-alpha, IFNgamma, interleukin (IL)-2, and arachidonic acid metabolites modulate IL-4-induced IgE synthesis similarly in healthy persons and in atopic dermatitis patients. Allergy 48 (3), 189–195. 1993

    Article  PubMed  CAS  Google Scholar 

  • Rivington, R. N., Boulet, L. P., Cote, J., Kreisman, H., Small, D. I., Alexander, M., Day, A., Harsanyi, Z., and Darke, A. C. Efficacy of Uniphyl, salbutamol, and their combination in asthmatic patients on high-dose inhaled steroids. Am.J.Respir.Crit Care Med. 151 (2 Pt 1), 325–332. 1995

    PubMed  CAS  Google Scholar 

  • Rivkin, I and Neutze, J. A. Influence of cyclic nucleotides and a phosphodiesterase inhibitor on in vitro human blood neutrophil chemotaxis. Arch.Int.Pharmacodyn.Ther. 228 (2), 196–204. 1977

    PubMed  CAS  Google Scholar 

  • Rossi, A. G., Cousin, J. M., Dransfield, I., Lawson, M. E, Chilvers, E. R., and Haslett, C. Agents that elevate cAMP inhibit human neutrophil apoptosis. Biochem.Biophys.Res.Commun. 217(3), 892–899. 26–12–1995

    Google Scholar 

  • Sagara, H., Fuiuda, T., Okada, T., Ishikawa, A., and Makino, S. Theophylline at therapeutic concentration suppresses PAF-induced upregulation of Mac-1 on human eosinophils. Clinical and Experimental Allergy, Supplement 26, 16–21. 1996

    CAS  Google Scholar 

  • Scherer, L. J., Diamond, R. A., and Rothenberg, E. V. Developmental regulation of cAMP signaling pathways in thymocyte development. Thymus 23, 231–257. 1994

    PubMed  CAS  Google Scholar 

  • Schmeichel, C. J. and Thomas, L. L. Methylxanthine bronchodilators potentiate multiple human neutrophil functions. J.Immunol. 138(6), 1896–1903. 15–3–1987

    Google Scholar 

  • Scordamaglia, A., Ciprandi, G., Ruffoni, S., Caria, M., Paolieri, F., Venuti, D., and Canonica, G. W. Theophylline and the immune response: in vitro and in vivo effects. Clin.Immunol.Immunopathol. 48 (2), 238–246. 1988

    Article  PubMed  CAS  Google Scholar 

  • Sherman, M. S., Lang, D. M., Matityahu, A., and Campbell, D. Theophylline improves measurements of respiratory muscle efficiency. Chest 110 (6), 1437–1442. 1996

    Article  PubMed  CAS  Google Scholar 

  • Shichijo, M., Shimizu, Y., Hiramatsu, K., Inagaki, N., Tagaki, K., and Nagai, H. Cyclic AMP-elevating agents inhibit mite-antigen-induced IL-4 and IL-13 release from basophil-enriched leukocyte preparation. Int.Arch.Allergy Immunol. 114 (4), 348–353. 1997

    Article  PubMed  CAS  Google Scholar 

  • Shohat, B., Volovitz, B., and Varsano, I. Induction of suppressor T cells in asthmatic children by theophylline treatment. Clin.Allergy 13 (5), 487–493. 1983

    Article  PubMed  CAS  Google Scholar 

  • Shute, J. K., Tenor, H., Church, M. K., and Holgate, S. T. Theophylline inhibits the release of eosinophil survival cytokines—Is Raf-1 the protein kinase A target? Clinical Experimental Allergy, Supplement 28 (3), 47–52. 1998

    CAS  Google Scholar 

  • Souness, J. E., Griffin, M., Maslen, C., Ebsworth, K., Scott, L. C., Pollock, K., Palfreyman, M. N., and Karlsson, J. A. Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNFa generation from human monocytes by interacting with a `low-affinity’ phosphodiesterase 4 conformer. Br.J.Pharmacol. 118, 649–658. 1996

    Article  PubMed  CAS  Google Scholar 

  • Spatafora, M., Chiappara, G., Merendino, A. M., D’Amico, D., Bellia, V, and Bonsignore, G. Theophylline suppresses the release of tumour necrosis factor-alpha by blood monocytes and alveolar macrophages. Eur.Respir.J. 7 (2), 223–228. 1994

    Article  PubMed  CAS  Google Scholar 

  • Spina, D., Ferlenga, P., Biasini, I., Moriggi, E., Marchini, E, Semeraro, C., and Page, C. P. The effect duration of selective phosphodiesterase inhibitors in the guinea-pig. Life Sci. 11, 953–965. 1998a

    Article  Google Scholar 

  • Spina, D., Landells, L. J., and Page, C. P. The role of phosphodiesterase isoenzymes in health and in atopic disease. August, T. Advances in Pharmacology. 33–89. 1998b. San Diego, Academic Press Inc

    Google Scholar 

  • Spoelstra, F. M., Berends, C., Dijkhuizen, B., De Monchy, J. G. R., and Kauffman, H. F. Effect of theophylline on CD1lb and L-selectin expression and density of eosinophils and neutrophils in vitro. European Respiratory Journal 12 (3), 585–591. 1998

    Article  PubMed  CAS  Google Scholar 

  • Steele, T. A. and Brahmi, Z. Phosphatidylinositol metabolism accompanies early activation events in tumor target cell-stimulated human natural killer cells. Cell.Immunol. 112, 402–443. 1988

    Article  PubMed  CAS  Google Scholar 

  • Sullivan, P., Bekir, S., Jaffar, Z., Page, C., Jeffery, P., and Costello, J. Anti-inflammatory effects of low-dose oral theophylline in atopic asthma [published erratum appears in Lancet 1994 Jun 11; 343(8911):15121. Lancet 343 (8904), 1006–1008. 1994

    Article  PubMed  CAS  Google Scholar 

  • Sung, S. S. and Walters, J. A. Increased cyclic AMP levels enhance IL-1 alpha and IL-1 beta mRNA expression and protein production in human myelomonocytic cell lines and monocytes. J.Clin.Invest. 88 (6), 1915–1923. 1991

    Article  PubMed  CAS  Google Scholar 

  • Tenor, H., Hatzelmann, A., Church, M. K., Schudt, C., and Shute, J. K. Effects of theophylline and rolipram on leukotriene C4 (LTC4) synthesis and chemotaxis of human eosinophils from normal and atopic subjects. Br.J.Pharmacol. 118, 1727–1735. 1996

    Article  PubMed  CAS  Google Scholar 

  • Thomas, P., Pugsley, J. A., and Stewart, J. H. Theophylline and salbutamol improve pulmonary function in patients with irreversible chronic obstructive pulmonary disease. Chest 101 (1), 160–165. 1992

    Article  PubMed  CAS  Google Scholar 

  • Thompson, P. B., Daughton, D., and Robbins, G. A. Intramural airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters. Am.Rev.Respir.Dis. 140, 1527–1537. 1989

    Article  PubMed  CAS  Google Scholar 

  • Tinkelman, D. G., Reed, C. E., Nelson, H. S., and Offord, K. P. Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Pediatrics 92 (1), 64–77. 1993

    PubMed  CAS  Google Scholar 

  • Turner, C. R., Esser, K. M., and Wheeldon, E. B. Therapeutic intervention in a rat model of ARDS: IV. Phosphodiesterase IV inhibition. Circ.Shock 39 (3), 237–245. 1993

    PubMed  CAS  Google Scholar 

  • Ukena, D., Harnest, U., Sakalauskas, R., Magyar, P., Vetter, N., Steffen, H., Leichtl, S., Rathgeb, F., Keller, A., and Steinijans, V. W. Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur.Respir.J. 10, 2754–2760. 1997

    Article  PubMed  CAS  Google Scholar 

  • Umut, S., Gemicioglu, B., Yildirim, N., Barlas, A., and Ozuner, Z. Effect of theophylline in chronic obstructive lung disease. Int.J Clin.Pharmacol.Ther.Toxicol. 30 (5), 149–152. 1992

    PubMed  CAS  Google Scholar 

  • van der Pouw, Kraan, Boeije, L. C., Smeenk, R. J., Wijdenes, J., and Aarden, L. A. Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. J.Exp.Med. 181 (2), 775–779. 1995

    Google Scholar 

  • Vanhaesebroeck, B., Jones, G. E., Allen, W. E., Zicha, D., Hooshmand-Rad, R., Sawyer, C., Wells, C., Waterfield, M. D., and Ridley, A. J. Distinct PI(3)Ks mediate mitogenic signalling and cell migration in macrophages. Nat.Cell Biol. 1 (1), 69–71. 1999

    Article  PubMed  CAS  Google Scholar 

  • Vanhaesebroeck, B., Welham, M. J., Kotani, K., Stein, R., Warne, P. H., Zvelebil, M. J., Higashi, K., Volinia, S., Downward, J., and Waterfield, M. D. P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc.Natl.Acad.Sci.U.S.A 94(9), 4330–4335. 294–1997

    Google Scholar 

  • Varriale, P. and Ramaprasad, S Aminophylline induced atrial fibrillation. Pacing Clin.Electrophysiol. 16 (10), 1953–1955. 1993

    Article  PubMed  CAS  Google Scholar 

  • Verghese, M. W., McConnell, R. T., Strickland, A. B., Gooding, R. C., Stimpson, S. A., Yarnall, D. P., Taylor, J. D., and Furdon, P. J. Differential regulation of human monocyte-derived TNF alpha and IL-1 beta by type IV cAMP-phosphodiesterase (cAMP-PDE) inhibitors. J.Pharmacol.Exp.Ther. 272 (3), 1313–1320. 1995

    PubMed  CAS  Google Scholar 

  • Viherluoto, J., Palkama, T., Silvennoinen, O., and Hurme, M. Cyclic adenosine monophosphate decreases the secretion, but not the cell-associated levels, of interleukin-1 beta in lipopolysaccharide-activated human monocytes. Scand.J.Immunol. 34 (1), 121–125. 1991

    Article  PubMed  CAS  Google Scholar 

  • Ward, A. J., McKenniff, M., Evans, J. M., Page, C. P., and Costello, J. F. Theophylline—an immunomodulatory role in asthma? Am.Rev.Respir.Dis. 147 (3), 518–523. 1993

    PubMed  CAS  Google Scholar 

  • Weinberger, M. and Hendeles, L. Theophylline in asthma. N.Engl.J.Med. 334(21), 1380–1388.23–5–1996

    Google Scholar 

  • Weston, M. C., Anderson, N., and Peachell, P. T. Effects of phosphodiesterase inhibitors on human lung mast cell and basophil function. Br.J.Pharmacol. 121 (2), 287–295. 1997

    Article  PubMed  CAS  Google Scholar 

  • Wolkove, N., Dajczman, E., Colacone, A., and Kreisman, H. The relationship between pulmonary function and dyspnea in obstructive lung disease. Chest 96 (6), 1247–1251. 1989

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi, Y., Hayashi, Y., Sugama, Y., Miura, Y., Kasahara, T., Kitamura, S., Torisu, M., Mita, S., Tominaga, A., and Takatsu, K. Highly purified murine interleukin 5 (IL–5) stimulates eosinophil function and prolongs in vitro survival. IL–5 as an eosinophil chemotactic factor. J.Exp.Med. 167(5), 1737–1742. 1–5–1988

    Google Scholar 

  • Yasui, K., Agematsu, K., Shinozaki, K., Hokibara, S., Nagumo, H., Nakazawa, T., and Komiyama, A. Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism. J.Leukoc.Biol. 67 (4), 529–535. 2000a

    PubMed  CAS  Google Scholar 

  • Yasui, K., Agematsu, K., Shinozaki, K., Hokibara, S., Nagumo, H., Yamada, S., Kobayashi, N., and Komiyama, A. Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions. J.Leukoc.Biol. 68 (2), 194–200. 2000b

    PubMed  CAS  Google Scholar 

  • Yasui, K., Hu, B., Nakazawa, T., Agematsu, K., and Komiyama, A. Theophylline accelerates human granulocyte apoptosis not via phosphodiesterase inhibition. Journal of Clinical Investigation 100 (7), 1677–1684. 1997

    Article  PubMed  CAS  Google Scholar 

  • Zocchi, M. R., Pardi, R., Gromo, G., Ferrero, E., Ferrero, M. E., Besana, C., and Rugarli, C. Theophylline induced non specific suppressor activity in human peripheral blood lymphocytes. J.Immunopharmacol. 7 (2), 217–234. 1985

    Article  PubMed  CAS  Google Scholar 

  • ZuWallack, R. L., Mahler, D. A., Reilly, D., Church, N., Emmett, A., Rickard, K., and Knobil, K. Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest 119 (6), 1661–1670. 2001

    Article  PubMed  CAS  Google Scholar 

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    N. A. Jones & C. P. Page

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    Clive P. Page

  2. National Heart & Lung Institute, Department of Thoracic Medicine, Imperial College, Dovehouse Street, SW3 6LY, London, UK

    Peter J. Barnes

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Jones, N.A., Page, C.P. (2004). Theophylline in the Treatment of Respiratory Disease. In: Page, C.P., Barnes, P.J. (eds) Pharmacology and Therapeutics of Asthma and COPD. Handbook of Experimental Pharmacology, vol 161. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-09264-4_3

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