Abstract
We evaluated the effect of exogenously administered recombinant human granulocyte-macrophage colony stimulating factor (rHu GM-CSF) on plasma lipid and lipoprotein concentrations in 28 patients undergoing bone marrow transplantation (BMT). Twenty-one received rHu GM-CSF during the immediate post transplantation period (group 1) and seven did not (group 2). All patients received intravenous hyperalimentation starting at the immediate post-transplantation period until 3–5 days post engraftment. Plasma lipids and lipoproteins, liver and renal function tests and blood counts were determined prior to BMT (baseline levels) and during the immediate and late post transplantation periods. In both groups, marked changes of plasma total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) concentrations were observed. During the immediate post transplantation period, TC levels decreased by 22.2% and 26.2% in groups 1 and 2, respectively. During the same period, HDL-C levels decreased by 41.4% and 37.5% in these two groups. At the late recovery phase TC and HDL-C resumed pre-treatment levels. These changes were in parallel to the fluctuations in total WBC counts. We conclude, therefore, that BMT has a significant transient effect on plasma lipids and lipoproteins. Although this response is unrelated to the exogenous administration of rHu GM-CSF it may be causally related to endogenous cytokines or other, yet unidentified, factors.
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Slavin, S. and Nagler, A. (1991) New developments in bone marrow transplantation.Curr. Opinion Oncol. 3, 254–71.
Nimer,S.D., Champlin, R.E. and Golde, D.W. (1988) Serum cholesterol-lowering activity of granulocyte-macrophage colony-stimulating factor.J. Am. Med. Assoc. 260, 3297–300.
Rifkin, R.M., Hersh, E.M. and Salmon, S.E. (1988) A phase I study of therapy with recombinant granulocyte-macrophage colony-stimulating factor administered by IV bolus or continuous infusion.Behring Inst. Mitt. 83, 125–33.
Ishibashi, S., Inaba, T., Shimano, H., Harada, K., Inoue, K., Mokuno, H., Mori, N., Gotoda, T., Takaku, F. and Yamada, N. (1990) Monocyte colony-stimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocytederived macrophages.J. Biol. Chem. 265, 14109–17.
Rajavashisth, T.B., Andalibi, A., Territo, M.C., Berliner, J.A., Navab, M., Fogelman, A.M. and Lusis, AJ. (1990) Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors modified low-density lipoproteins.Nature 344, 254–7.
Stoudemire, J. and Garnick, M.B. (1991) Effects of recombinant human macrophage colony-stimulating factor on plasma cholesterol levels.Blood 77, 750–5.
Takahashi, M., Nikkuni, K., Moriyama, Y. and Shibata, A. (1991) GM-CSF-mediated impairment of liver to synthesize albumin, cholinesterase, and cholesterol.Am. J. Hemat. 36, 1213–4.
Zukerman, S.H., Evans, G.F. and O’Neal, L. (1992) Cytokine regulation of macrophage apo E secretion: opposing effects of GM-CSF and TGF-beta.Atherosclerosis 96, 203–14.
Stopeck, A.T., Nicholson, A.C., Mancini, F.P. and Hajjar, D.P. (1993) Cytokine regulation of low density lipoprotein receptor gene transcription in HepG2 cells.J. Biol. Chem. 268, 17489–94.
Goldstein, J.L. and Brown, M.S. (1989) Familial hypercho- lesterolemia. In: C.R. Scriver, A.L. Beaudet, W.S. Sly and D. Valle (eds)The Metabolic Basis of Inherited Disease, 6th edn, pp. 1215–50. New York: McGraw-Hill.
Esterbauer, H. and J’rgens, G. (1993) Mechanistic and genetic aspects of susceptibility of LDL to oxidation.Curr. Opinion Lipidol. 4, 114–24.
Ishibashi, T., Yokoyama, K., Shindo, J., Hamazaki, Y., Endo, Y., Sato, T., Takahashi, S., Kawarabayasi, Y., Shiomi, M., Yamamoto, T. and Maruyama, Y. (1994) Potent cholesterol-lowering effect by human granulocyte- macrophage colony-stimulating factor in rabbits.Arterioscler. Thromb. 14, 1534–41.
Yamamoto, T., Bishop, R.W., Brown, M.S., Goldstein, J.L. and Russell, D.W. (1986) Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit.Science 232, 1230–7.
Holler, E., Kolb, H.J., Mîller, A., Kempeni, J., Liesenfeld, S., Pechumer, H., Lehmacher, W., Ruckdeschel, G., Gleixner, B., Riedner, C., Ledderose, G., Brehm, G., Mitterm’ller, J. and Wilmanns, W. (1990) Increased serum levels of tumor necrosis factor precede major complications of bone marrow transplantation.Blood 75, 1011–16.
Naparstek, E., Hardan, Y., Ben-Shahar, M., Nagler, A., Or, R., Mumcuoglu, M., Weiss, L., Samuel, S. and Slavin, S. (1992) Enhanced marrow recovery by short perincubation of marrow allografts with human recombinant interleukin- 3 and granulocyte-macrophage colony-stimulating factor.Blood 7, 1673–8.
Klapholz, L., Ackerstein, A., Goldenhersh, M.A., Vardy, D. and Nagler, A. (1993) Local cutaneous reaction induced by subcutaneous interleukin-2 and interferon alpha-2a immunotherapy following ABMT.Bone Marrow Transplant. 11, 443–6.
Friedewald, W.T., Levy, R.I. and Fredrickson, D.S. (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the preparative ultra- centrifuge.Clin. Chem. 18, 499–502.
Winer, B.J. (1969)Statistical Principles in Experimental Design. New York: McGraw-Hill.
Sammalkorpi, K., Valtonen, V., Kettula, Y. NikkiN, E. and Taskinen, M. (1988) Changes in serum lipoprotein pattern induced by acute infections.Metabolism 37, 859–65.
Evans, R., Argiläs, J. and Williamson, D. (1989) Metabolic effects of tumor necrosis factor-γ (cachectin) and interleu- kin-1.Clin. Sci. 77, 357–64.
Foa, R., Guarini, A., Francia de Celle, P., Trentin, L., GillioTos, A., Bellone, G., Carbone, A., Attisano, C., Massaia, M., Raspadori, D., Pizzolo, G., Chisesi, T., Lauria, F. and Semenzato, G. (1992) Constitutive production of tumor necrosis factor-alpha in hairy cell leukemia: possible role in the pathogenesis of the cytopenia(s) and effect of treatment with interferon-alpha.J. Clin. Oncol. 10, 954–9.
Grunfeld, C., Kotier, D., Shigenaga, J., Doerrler, W., Tierney, A., Wang, J., Pierson, R. and Feingold, K. (1991) Circulating interferon- and hypertriglyceridemia in the acquired immunodeficiency syndrome.Am. J. Med. 90, 154–62.
Grunfeld, C. and Feingold, K. (1992) Metabolic disturbances and wasting in the acquired immunodeficiency syndrome.N. Engl. J. Med. 327, 329–37.
Riikonen, P., Saarinen, U., Teppo, A., Metsarinne, K., Fyhrquist, F. and Jalanko, H. (1988) Cytokine and acute- phase reactant levels in serum of children with cancer admitted for fever and neutropenia.J. Infect. Dis. 166, 432–6.
Toti, F.M., Dieckmann, B., Beutler, B., Cerami, A. and Ringold, G.M. (1985) A macrophage factor inhibits adipo- cyte gene expression: anin vitro model of cachexia.Science 229, 867–9.
Grunfeld, C., Wilking, H., Neese, R., Gavin, L., Moser, A., Gulli, R., Serio, M.K. and Feingold, K. (1989) Persistence of the hypertriglyceridemic effect of tumor necrosis factor despite development of tachyphylaxis to its anorectic/ cachectic effects in rats.Cancer Res. 49, 2554–60.
Feingold, K., Soued, M., Serio, K., Moser, A., Dinarello, C. and Grunfeld, C. (1989) Multiple cytokines stimulate hepatic lipid synthesisin vivo.Endocrinology 125, 267–74.
Jonasson, L., Hansson, G., Bondijers, G., Noe, L. and Etienne, J. (1990) Interferon-gamma inhibits lipoprotein lipase in human monocyte-derived macrophages.Biochim. Biophys. Acta 1053, 43–8.
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Dann, E.J., Friedlander, Y., Leitersdorf, E. et al. The modulation of plasma lipids and lipoproteins during bone marrow transplantation is unrelated to exogenously administered recombinant human granulocyte-mnonocyte colony-stimulating factor (rHu GM-CSF). Med Oncol 13, 81–86 (1996). https://doi.org/10.1007/BF02993857
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DOI: https://doi.org/10.1007/BF02993857