Skip to main content
SpringerLink
Log in

Monitoring inflammation in CF

Cytokines

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

In cystic fibrosis (CF), chronic airway infection and neutrophil-dominated airway inflammation lead to progressive lung disease. Cytokines play an important role in the inflammatory response. Evidence suggests that cytokine production is altered or dysregulated in CF. Moreover, polymorphisms in cytokines may be linked to disease severity by acting as modifier genes. This article reviews the current state of knowledge regarding individual cytokines and CF lung disease, with an eye towards the possibility that cytokines may be used as outcome measures in clinical trials in CF. In addition, cytokines may eventually serve as targets for novel anti-inflammatory therapies in CF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Welsh, M.J., Ramsey, B.W., Accurso, F.J., and Cutting, G.R. (2001), in The Metabolic and Molecular Bases of Inherited Disease, Scriver, C.R., Beaudet, A.L., Valle, D., and Sly, W.S., eds., McGraw Hill, New York, pp. 521–588.

    Google Scholar 

  2. Konstan, M.W. and Berger, M. (1997), Pediatr. Pulmonol. 24, 137–142.

    Article  PubMed  CAS  Google Scholar 

  3. Armstrong, D.S., Grimwood, K., Carzino, R., Carlin, J.B., Olinsky, A., and Phelan, P.D. (1995), Br. Med. J. 310, 1571–1572.

    CAS  Google Scholar 

  4. Khan, T.Z., Wagener, J.S., Bost, T., Martinez, J., Accurso, F.J., and Riches, D.W. (1995), Am. J. Respir. Crit. Care Med. 151, 1075–1082.

    PubMed  CAS  Google Scholar 

  5. Balough, K., McCubbin, M., Weinberger, M., Smits, W., Ahrens, R., and Fick, R. (1995), Pediatr. Pulmonol. 20, 63–70.

    Article  PubMed  CAS  Google Scholar 

  6. Abman, S.H., Ogle, J.W., Harbeck, R.J., Butler-Simon, N., Hammond, K.B., and Accurso, F.J. (1991), J. Pediatr. 119, 211–217.

    Article  PubMed  CAS  Google Scholar 

  7. Smith, A.L., Ramsey, B., Redding, G., and Haas, J. (1989), Acta Paediatr. Scand. Suppl. 363, 31–36.

    PubMed  CAS  Google Scholar 

  8. Glligan, P.H. (1991), Clin. Microbiol. Rev. 4, 35–51.

    Google Scholar 

  9. Burns, J.L., Emerson, J., Stapp, J.R., Yim, D.L., Krzewinski, J., Louden, L., et al. (1998), Clin. Infect. Dis. 27, 158–163.

    PubMed  CAS  Google Scholar 

  10. Doring, G. (1994), Am. J. Respir. Crit. Care Med. 150, S114-S117.

    PubMed  CAS  Google Scholar 

  11. Bruce, M.C., Poncz, L., Klinger, J.D., Stern, R.C., Tomashefski, J.F., Jr., and Dearborn, D.G. (1985), Am. Rev. Respir. Dis. 132, 529–535.

    PubMed  CAS  Google Scholar 

  12. Tosi, M.F., Zakem, H., and Berger, M. (1990), J. Clin. Investig. 86, 300–308.

    PubMed  CAS  Google Scholar 

  13. Hubbard, R.C., Fells, G., Gadek, J., Pacholok, S., Humes, J., and Crystal, R.G. (1991), J. Clin. Investig. 88, 891–897.

    PubMed  CAS  Google Scholar 

  14. Sommerhoff, C.P., Nadel, J.A., Basbaum, C.B., and Caughey, G.H. (1990), J. Clin. Investig. 85, 682–689.

    PubMed  CAS  Google Scholar 

  15. Nakamura, H., Yoshimura, K., McElvaney, N.G., and Crystal, R.G. (1992), J. Clin. Investig, 89, 1478–1484.

    PubMed  CAS  Google Scholar 

  16. Wilmott, R.W., Kassab, J.T., Kilian, P.L., Benjamin, W.R., Douglas, S.D., and Wood, R.W. (1990), Am. Rev. Respir. Dis. 142, 365–368.

    PubMed  CAS  Google Scholar 

  17. Bonfield, T.L., Panuska, J.R., Konstan, M.W., Hilliard, K.A., Hilliard, J.B., Ghnaim, H., et al. (1995), Am. J. Respir. Crit. Care Med. 152, 2111–2118.

    PubMed  CAS  Google Scholar 

  18. Smith, J.J., Travis, S.M., Greenberg, E.P., and Welsh, M.J. (1996), Cell 85, 229–236.

    Article  PubMed  CAS  Google Scholar 

  19. Goldman, M.J., Anderson, G.M., Stolzenberg, E.D., Kari, U.P., Zasloff, M., and Wilson, J.M. (1997), Cell 88, 553–560.

    Article  PubMed  CAS  Google Scholar 

  20. Matsui, H., Grubb, B.R., Tarran, R., Randell, S.H., Gatzy, J.T., Davis, C.W., et al. (1998), Cell 95, 1005–1015.

    Article  PubMed  CAS  Google Scholar 

  21. Ma, W. Korngreen, A., Uzlaner, N., Priel, Z., and Silberberg, S.D. (1999), Nature 400, 894–897.

    Article  PubMed  CAS  Google Scholar 

  22. Saiman, L. and Prince, A. (1993), J. Clin. Investig. 92, 1875–1880.

    PubMed  CAS  Google Scholar 

  23. Pier, G.B., Grout, M., Zaidi, T.S., Olsen, J.C., Johnson, L.G., Yankaskas, J.R., et al. (1996), Science 271, 64–67.

    Article  PubMed  CAS  Google Scholar 

  24. Engelhardt, J.F., Yankaskas, J.R., Ernst, S.A., Yang, Y., Marino, C.R., Boucher, R.C., et al. (1992), Nat. Genet. 2, 240–248.

    Article  PubMed  CAS  Google Scholar 

  25. DiMango, E., Ratner, A.J., Bryan, R., Tabibi, S., and Prince, A. (1998), J. Clin. Investig. 101, 2598–2605.

    PubMed  CAS  Google Scholar 

  26. Tirouvanziam, R., de Bentzmann, S., Hubeau, C., Hinnrasky, J., Jacquot, J., Peault, B., et al. (2000), Am. J. Respir. Cell Mol. Biol. 23, 121–127.

    PubMed  CAS  Google Scholar 

  27. Armstrong, D.S., Grimwood, K., Carlin, J.B., Carzino, R., Gutierrez, J.P., Hull, J., et al. (1997), Am. J. Respir. Crit. Care Med. 156, 1197–1204.

    PubMed  CAS  Google Scholar 

  28. Scheid, P., Kempster, L., Griesenbach, U., Davies, J.C., Dewar, A., Weber, P.P., et al. (2001), Eur. Respir. J. 17, 27–35.

    Article  PubMed  CAS  Google Scholar 

  29. Durum, S.K. and Muegge, K. (1996), in Clinical Immunology: Principles and Practice, Rich, R.R., ed., Mosby, St. Louis, pp. 350–362.

    Google Scholar 

  30. Bonfield, T.L., Konstan, M.W., Burfeind, P., Panuska, J.R., Hilliard, J.B., and Berger, M. (1995), Am. J. Respir. Cell. Mol. Biol. 13, 257–261.

    PubMed  CAS  Google Scholar 

  31. Kammouni, W., Figarella, C., Marchand, S., and Merten, M. (1997), Infect. Immun. 65, 5176–5183.

    PubMed  CAS  Google Scholar 

  32. Tabary, O., Zahm, J.M., Hinnrasky, J., Couetil, J.P., Cornillet, P., Guenounou, M., et al. (1998) Am. J. Pathol. 153, 921–930.

    PubMed  CAS  Google Scholar 

  33. Bonfield, T.L., Konstan, M.W., and Berger, M. (1999), J. Allergy Clin. Immunol. 104, 72–78.

    Article  PubMed  CAS  Google Scholar 

  34. Tabary, O., Escotte, S., Couetil, J.P., Hubert, D., Dusser, D., Puchelle, E., et al. (2000), J. Immunol. 164, 3377–3384.

    PubMed  CAS  Google Scholar 

  35. Venkatakrishnan, A., Stecenko, A.A., King, G., Blackwell, T.R., Brigham, K.L., Christman, J.W., et al. (2000), Am. J. Respir. Cell Mol. Biol. 23, 396–403.

    PubMed  CAS  Google Scholar 

  36. Stecenko, A.A., King, G., Torii, K., Breyer, R.M., Dworski, R., Blackwell, T.S., et al. (2001), Inflammation 25, 145–155.

    Article  PubMed  CAS  Google Scholar 

  37. Moss, R.B., Bocian, R.C., Hsu, Y.P., Dong, Y.J., Kemna, M., Wei, T., et al. (1996), Clin. Exp. Immunol. 106, 374–388.

    Article  PubMed  CAS  Google Scholar 

  38. Moss, R.B., Hsu, Y.P., and Olds, L. (2000), Clin. Exp. Immunol. 120, 518–525.

    Article  PubMed  CAS  Google Scholar 

  39. Mosmann, T. (1996), in Clinical Immunology: Principles and Practice, Rich, R.R., ed., Mosby, St. Louis, pp. 217–230.

    Google Scholar 

  40. Wewers, M.D., Gadek, J.E., and Marsh, C.B. (1997) in The Lung: Scientific Foundations, Crystal, R.G. and West, J.B., eds., Lippincott-Raven Publishers, Philadelphia, pp. 117–129.

    Google Scholar 

  41. Le, J. and Vilcek, J. (1987), Lab. Investig. 56, 234–248.

    PubMed  CAS  Google Scholar 

  42. Suter, S., Schaad, U.B., Roux-Lombard, P., Girardin, E., Grau, G., and Dayer, J.M. (1989), Am. Rev. Respir. Dis. 140, 1640–1644.

    PubMed  CAS  Google Scholar 

  43. Levy, E., Gurbindo, C., Lacaille, F., Paradis, K., Thibault, L., and Seidman, E. (1993), Pediatr. Res. 34, 162–166.

    Article  PubMed  CAS  Google Scholar 

  44. Brown, M.A., Morgan, W.J., Finley, P.R., and Scuderi, P. (1991), Pediatr. Pulmonol. 10, 86–91.

    Article  PubMed  CAS  Google Scholar 

  45. Kronborg, G., Hansen, M.B., Svenson, M., Fomsgaard, A., Hoiby, N., and Bendtzen, K. (1993), Pediatr. Pulmonol. 15, 292–297.

    Article  PubMed  CAS  Google Scholar 

  46. Elborn, J.S., Nixon, L., Bell, S.C., and Shale, D.J. (1994), Pediatr. Pulmonol. 17, 411–412.

    Article  PubMed  CAS  Google Scholar 

  47. Wilmott, R.W. (2000), in Cytokines in Pulmonary Disease: Infection and Inflammation, Nelson, S., and Martin, T.R., eds., Marcel Dekker, Inc., New York, pp. 307–330.

    Google Scholar 

  48. Norman, D., Elborn, J.S., Cordon, S.M., Rayner, R.J., Wiseman, M.S., Hiller, E.J., et al. (1991), Thorax 46, 91–95.

    PubMed  CAS  Google Scholar 

  49. Wilmott, R.W., Frenzke, M., Kociela, V., and Peng, L. (1994), Pediatr. Pulmonol. 18, 21–27.

    Article  PubMed  CAS  Google Scholar 

  50. Elborn, J.S., Cordon, S.M., Parker, D., Delamere, F.M., and Shale, D.J. (1993), Respir. Med. 87, 603–607.

    Article  PubMed  CAS  Google Scholar 

  51. Elborn, J.S., Cordon, S.M., Western, P.J., Macdonald, I.A., and Shale, D.J. (1993) Clin. Sci. (Colch.) 85, 563–568.

    CAS  Google Scholar 

  52. Salva, P.S., Doyle, N.A., Graham, L., Eigen, H., and Doerschuk, C.M. (1996), Pediatr. Pulmonol. 21, 11–19.

    Article  PubMed  CAS  Google Scholar 

  53. Osika, E., Cavaillon, J.M., Chadelat, K., Boule, M., Fitting, C., Tournier, G., et al. (1999), Eur. Respir. J. 14, 339–346.

    Article  PubMed  CAS  Google Scholar 

  54. Wolter, J.M., Rodwell, R.L., Bowler, S.D., and McCormack, J.G. (1999), Clin. Diagn. Lab. Immunol. 6, 260–265.

    PubMed  CAS  Google Scholar 

  55. Pukhalsky, A.L., Kapranov, N.I., Kalashnikova, E.A., Shmarina, G.V., Shabalova, L.A., Kokarovtseva, S.N., et al. (1999), Mediat. Inflamm. 8, 159–167.

    Article  CAS  Google Scholar 

  56. Karpati, F., Hjelte, F.L., and Wretlind, B. (2000), Scand. J. Infect. Dis. 32, 75–79.

    Article  PubMed  CAS  Google Scholar 

  57. Balfour-Lynn, I.M., Klein, N.J., and Dinwiddie, R. (1997), Arch. Dis. Child. 77, 124–130.

    Article  PubMed  CAS  Google Scholar 

  58. Greally, P., Hussain, M.J., Cook, A.J., Sampson, A.P., Piper, P.J., and Price, J.F. (1993), Arch. Dis. Child. 68, 389–392.

    PubMed  CAS  Google Scholar 

  59. Greally, P., Hussain, M.J., Vergani, D., and Price, J.F. (1993), Arch. Dis. Child. 68, 785–787.

    PubMed  CAS  Google Scholar 

  60. Greally, P., Hussain, M.J., Vergani, D., and Price, J.F. (1994), Arch. Dis. Child. 71, 35–39.

    PubMed  CAS  Google Scholar 

  61. Ulich, T.R., Yin, S., Guo, K., Yi, E.S., Remick, D., and del Castillo, J. (1991), Am. J. Pathol. 138, 1097–1101.

    PubMed  CAS  Google Scholar 

  62. Tilg, H., Dinarello, C.A., and Mier, J.W. (1997), Immunol. Today 18, 428–432.

    Article  PubMed  CAS  Google Scholar 

  63. Kube, D., Sontich, U., Fletcher, D., and Davis, P.B. (2001), Am. J. Physiol. Lung Cell Mol. Physiol. 280, L493-L502.

    PubMed  CAS  Google Scholar 

  64. McElvaney, N.G. and Crystal, R.G. (1995), Nat. Med. 1, 182–184.

    Article  PubMed  CAS  Google Scholar 

  65. Ruiz, F.E., Clancy, J.P., Perricone, M.A., Bebok, Z., Hong, J.S., Cheng, S.H., et al. (2001), Hum. Gene Ther. 12, 751–761.

    Article  PubMed  CAS  Google Scholar 

  66. Nixon, L.S., Yung, B., Bell, S.C., Elborn, J.S., and Shale, D.J. (1998), Am. J. Respir. Crit. Care Med. 157, 1764–1769.

    PubMed  CAS  Google Scholar 

  67. Ionescu, A.A., Nixon, L.S., Evans, W.D., Stone, M.D., Lewis-Jenkins, V., Chatham, K., et al. (2000), Am. J. Respir. Crit. Care Med. 162, 789–794.

    PubMed  CAS  Google Scholar 

  68. Aris, R.M., Stephens, A.R., Ontjes, D.A., Denene, B.A., Lark, R.K., Hensler, M.B., et al. (2000), Am. J. Respir. Crit. Care Med. 162, 1674–1678.

    PubMed  CAS  Google Scholar 

  69. Noah, T.L., Black, H.R., Cheng, P.W., Wood, R.E., and Leigh, M.W. (1997), J. Infect. Dis. 175, 638–647.

    PubMed  CAS  Google Scholar 

  70. Fahy, J.V., Kim, K.W., Liu, J., and Boushey, H.A. (1995), J. Allergy Clin. Immunol. 95, 843–852.

    Article  PubMed  CAS  Google Scholar 

  71. Richman-Eisenstat, J.B., Jorens, P.G., Hebert, C.A., Ueki, I., and Nadel, J.A. (1993), Am. J. Physiol. 264, L413-L418.

    PubMed  CAS  Google Scholar 

  72. Mikami, M., Llewellyn-Jones, C.G., Bayley, D., Hill, S.L., and Stockley, R.A. (1998), Am. J. Respir. Crit. Care Med. 157, 723–728.

    PubMed  CAS  Google Scholar 

  73. McElvaney, N.G., Nakamura, H., Birrer, P., Hebert, C.A., Wong, W.L., Alphonso, M., et al. (1992), J. Clin. Investig. 90, 1296–1301.

    Article  PubMed  CAS  Google Scholar 

  74. Dean, T.P., Dai, Y., Shute, J.K., Church, M.K., and Warner J.O. (1993), Pediatr. Res. 34, 159–161.

    Article  PubMed  CAS  Google Scholar 

  75. Hull, J., Skinner, W., Robertson, C., and Phelan, P. (1998), Am. J. Respir. Crit. Care Med. 157, 10–14.

    PubMed  CAS  Google Scholar 

  76. Muhlebach, M.S., Stewart, P.W., Leigh, M.W., and Noah, T.L. (1999), Am. J. Respir. Crit. Care Med. 160, 186–191.

    PubMed  CAS  Google Scholar 

  77. Francoeur, C. and Denis, M. (1995), Inflammation 19, 587–598.

    Article  PubMed  CAS  Google Scholar 

  78. Shah, P.L., Scott, S.F., Knight, R.A., and Hodson, M.E. (1996), Eur. Respir. J. 9, 531–534.

    Article  PubMed  CAS  Google Scholar 

  79. Koller, D.Y., Nething, I., Otto, J., Urbanek, R., and Eichler, I. (1997), Am. J. Respir. Crit. Care Med. 155, 1050–1054.

    PubMed  CAS  Google Scholar 

  80. Sagel, S.D., Kapsner, R., Osberg, I., Sontag, M.K., and Accurso, F.J. (2001), Am. J. Respir. Crit. Care Med. 164, 1425–1431.

    PubMed  CAS  Google Scholar 

  81. Cunningham, S., McColm, J.R., Ho, L.P., Greening, A.P., and Marshall, T.G. (2000), Eur. Respir. J. 15, 955–957.

    Article  PubMed  CAS  Google Scholar 

  82. Ramsey, B.W., Boat, T.F., and for the Consensus Group. (1994), J. Pediatr. 124, 177–192.

    PubMed  CAS  Google Scholar 

  83. Rochat, T., Pastore, F.D., Schlegel-Haueter, S.E., Filthuth, I., Auckenthaler, R., Belli, D., et al. (1996), Eur. Respir. J. 9, 2200–2206.

    Article  PubMed  CAS  Google Scholar 

  84. Sawa, T., Corry, D.B., Gropper, M.A., Ohara, M., Kurahashi, K., and Wiener-Kronish, J.P. (1997), J. Immunol. 159,2858–2866.

    PubMed  CAS  Google Scholar 

  85. Chmiel, J.F., Konstan, M.W., Knesebeck, J.E., Hilliard, J.B., Bonfield, T.L., Dawson, D.V., et al. (1999), Am. J. Respir. Crit. Care Med. 160, 2040–2047.

    PubMed  CAS  Google Scholar 

  86. Asano, K., Chee, C.B., Gaston, B., Lilly, C.M., Gerard, C., Drazen, J.M., et al. (1994), Proc. Natl. Acad. Sci. USA 91, 10,089–10,093.

    Article  CAS  Google Scholar 

  87. Kelley, T.J. and Elmer, H.L. (2000), J. Clin. Investig. 106, 403–410.

    PubMed  CAS  Google Scholar 

  88. Cash, H.A., Woods, D.E., McCullough, B., Johanson, W.G., Jr., and Bass, J.A. (1979), Am. Rev. Respir. Dis. 119, 453–459.

    PubMed  CAS  Google Scholar 

  89. Moser, C., Johansen, H.K., Song, Z., Hougen, H.P., Rygaard, J., and Hoiby, N (1997), APMIS 105, 838–842.

    Article  PubMed  CAS  Google Scholar 

  90. Johansen, H.K., Hougen, H.P., Rygaard, J., and Hoiby, N. (1996), Clin. Exp. Immunol. 103, 212–218.

    Article  PubMed  CAS  Google Scholar 

  91. Moser, C., Kjaergaard, S., Pressler, T., Kharazmi, A., Koch, C., and Hoiby, N. (2000), APMIS 108, 329–335.

    Article  PubMed  CAS  Google Scholar 

  92. Wojnarowski, C., Frischer, T., Hofbauer, E., Grabner, C., Mosgoeller, W., Eichler, I., et al. (1999), Eur. Respir. J. 14, 1136–1144.

    Article  PubMed  CAS  Google Scholar 

  93. Rosensweig, J.N., Omori, M., Page, K., Potter, C.J., Perlman, E.J., Thorgeirsson, S.S., et al. (1998), Pediatr. Res. 44, 402–409.

    Article  PubMed  CAS  Google Scholar 

  94. Strieter, R.M. and Kunkel, S.L. (1997), in The Lung: Scientific Foundations, Crystal, R.G. and West, J.B., eds., Lippincott-Raven Publishers, Philadelphia, pp. 155–186.

    Google Scholar 

  95. Schwiebert, L.M., Estell, K., and Propst, S.M. (1999), Am. J. Physiol. 276, C700-C710.

    PubMed  CAS  Google Scholar 

  96. Hull, J. and Thomson, A.H. (1998), Thorax 53, 1018–1021.

    Article  PubMed  CAS  Google Scholar 

  97. Arkwright, P.D., Laurie, S., Super, M., Pravica, V., Schwarz, M.J., Webb, A.K., et al. (2000), Thorax 55, 459–462.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Children's Hospital, University of Colorado Health Sciences Center, 1056 E. 19th Ave., Box B395, 80218, Denver, CO

    Scott D. Sagel & Frank J. Accurso

Authors
  1. Scott D. Sagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank J. Accurso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott D. Sagel.

Additional information

This research was supported by the Cystic Fibrosis Foundation, the Mike McMorris Cystic Fibrosis Center, and Grant #M01 RR00069, General Clinical Research Centers Program, NCRR, NIH.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sagel, S.D., Accurso, F.J. Monitoring inflammation in CF. Clinic Rev Allerg Immunol 23, 41–57 (2002). https://doi.org/10.1385/CRIAI:23:1:041

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/CRIAI:23:1:041

Index Entries

Search

Navigation