Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1983 Dec;42(3):997–1005. doi: 10.1128/iai.42.3.997-1005.1983

Effect of ibuprofen on fever and metabolic changes induced by continuous infusion of leukocytic pyrogen (interleukin 1) or endotoxin.

J Sobrado, L L Moldawer, B R Bistrian, C A Dinarello, G L Blackburn
PMCID: PMC264398  PMID: 6358043

Abstract

Many of the metabolic sequelae to infection and inflammation, such as fever, trace mineral redistribution, skeletal muscle catabolism, and the acute-phase protein response, are mediated by leukocytic pyrogen (interleukin 1). In the anterior hypothalamus and in skeletal muscles leukocytic pyrogen appears to induce the synthesis of prostaglandin E2 which mediates fever and skeletal protein catabolism. It is unclear whether any additional metabolic responses to leukocytic pyrogen result from prostaglandin production. This study was undertaken to investigate the ability of ibuprofen, a specific cyclooxygenase inhibitor, to alter protein and trace metal responses to leukocytic pyrogen or endotoxin when given in quantities sufficient to block the febrile response. In guinea pigs given continuous infusions of leukocytic pyrogen or endotoxin, a 0.6 to 0.8 degrees C fever was observed within 4 h, and zinc and iron concentrations in serum fell by 63 to 78% (P less than 0.01). Rates of whole body amino acid appearance, oxidation, and incorporation into protein were all significantly increased by leukocytic pyrogen and endotoxin treatment, (P less than 0.05) as were the fractional hepatic and seromucoid protein synthesis rates in leukocytic pyrogen-treated animals (P less than 0.01). Muscle protein synthesis was unchanged. Although pretreatment with infusions of ibuprofen completely ablated the febrile response to leukocytic pyrogen and endotoxin, decreases in zinc and iron concentrations in serum and leukocytosis were unaffected. Overall increases in whole body amino acid kinetics induced by leukocytic pyrogen or endotoxin were only minimally affected by ibuprofen. We concluded that treatment with prostaglandin synthesis inhibitor ibuprofen did not affect whole body trace metal, hematological, or hepatic acute-phase-induced responses to leukocytic pyrogen or endotoxin, either because these responses are prostanoid independent or because they are only partially mediated by eicosanoid products.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baracos V., Rodemann H. P., Dinarello C. A., Goldberg A. L. Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1). A mechanism for the increased degradation of muscle proteins during fever. N Engl J Med. 1983 Mar 10;308(10):553–558. doi: 10.1056/NEJM198303103081002. [DOI] [PubMed] [Google Scholar]
  2. Beisel W. R., Goldman R. F., Joy R. J. Metabolic balance studies during induced hyperthermia in man. J Appl Physiol. 1968 Jan;24(1):1–10. doi: 10.1152/jappl.1968.24.1.1. [DOI] [PubMed] [Google Scholar]
  3. Bernheim H. A., Gilbert T. M., Stitt J. T. Prostaglandin E levels in third ventricular cerebrospinal fluid of rabbits during fever and changes in body temperature. J Physiol. 1980 Apr;301:69–78. doi: 10.1113/jphysiol.1980.sp013189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Birkhahn R. H., Long C. L., Fitkin D., Geiger J. W., Blakemore W. S. Effects of major skeletal trauma on whole body protein turnover in man measured by L-[1,14C]-leucine. Surgery. 1980 Aug;88(2):294–300. [PubMed] [Google Scholar]
  5. Bullen J. J. The significance of iron in infection. Rev Infect Dis. 1981 Nov-Dec;3(6):1127–1138. doi: 10.1093/clinids/3.6.1127. [DOI] [PubMed] [Google Scholar]
  6. Dale D. C., Fauci A. S., Guerry D I. V., Wolff S. M. Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone. J Clin Invest. 1975 Oct;56(4):808–813. doi: 10.1172/JCI108159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dinarello C. A., Bendtzen K., Wolff S. M. Studies on the active site of human leukocytic pyrogen. Inflammation. 1982 Mar;6(1):63–78. doi: 10.1007/BF00910720. [DOI] [PubMed] [Google Scholar]
  8. Dinarello C. A., Renfer L., Wolff S. M. Human leukocytic pyrogen: purification and development of a radioimmunoassay. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4624–4627. doi: 10.1073/pnas.74.10.4624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dinarello C. A., Renfer L., Wolff S. M. The production of antibody against human leukocytic pyrogen. J Clin Invest. 1977 Aug;60(2):465–472. doi: 10.1172/JCI108797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dinarello C. A., Wolff S. M. Molecular basis of fever in humans. Am J Med. 1982 May;72(5):799–819. doi: 10.1016/0002-9343(82)90548-4. [DOI] [PubMed] [Google Scholar]
  11. Farrar W. L., Mizel S. B., Farrar J. J. Participation of lymphocyte activating factor (Interleukin 1) in the induction of cytotoxic T cell responses. J Immunol. 1980 Mar;124(3):1371–1377. [PubMed] [Google Scholar]
  12. Feldberg W. The Ferrier Lecture, 1974. Body temperature and fever: changes in our views during the last decade. Proc R Soc Lond B Biol Sci. 1975 Nov 18;191(1103):199–229. doi: 10.1098/rspb.1975.0124. [DOI] [PubMed] [Google Scholar]
  13. Garlick P. J., Millward D. J., James W. P. The diurnal response of muscle and liver protein synthesis in vivo in meal-fed rats. Biochem J. 1973 Dec;136(4):935–945. doi: 10.1042/bj1360935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jacobs E. R., Soulsby M. E., Bone R. C., Wilson F. J., Jr, Hiller F. C. Ibuprofen in canine endotoxin shock. J Clin Invest. 1982 Sep;70(3):536–541. doi: 10.1172/JCI110645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kampschmidt R. F., Pulliam L. A., Upchurch H. F. The activity of partially purified leukocytic endogenous mediator in endotoxin-resistant C3H/HeJ mice. J Lab Clin Med. 1980 Apr;95(4):616–623. [PubMed] [Google Scholar]
  16. Kampschmidt R. F., Upchurch H. F. Neutrophil release after injections of endotoxin or leukocytic endogenous mediator into rats. J Reticuloendothel Soc. 1980 Aug;28(2):191–201. [PubMed] [Google Scholar]
  17. Klempner M. S., Dinarello C. A., Henderson W. R., Gallin J. I. Stimulation of neutrophil oxygen-dependent metabolism by human leukocytic pyrogen. J Clin Invest. 1979 Oct;64(4):996–1002. doi: 10.1172/JCI109566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kluger M. J., Ringler D. H., Anver M. R. Fever and survival. Science. 1975 Apr 11;188(4184):166–168. [PubMed] [Google Scholar]
  19. Moldawer L. L., Bistrian B. R., Sobrado J., Blackburn G. L. Muscle proteolysis in sepsis or trauma. N Engl J Med. 1983 Aug 25;309(8):494–495. doi: 10.1056/NEJM198308253090814. [DOI] [PubMed] [Google Scholar]
  20. Moldawer L. L., O'Keefe S. J., Bothe A., Jr, Bistrian B. R., Blackburn G. L. In vivo demonstration of nitrogen-sparing mechanisms for glucose and amino acids in the injured rat. Metabolism. 1980 Feb;29(2):173–180. doi: 10.1016/0026-0495(80)90143-2. [DOI] [PubMed] [Google Scholar]
  21. Neuhaus O. W., Balegno H. F., Chandler A. M. Induction of plasma protein synthesis in response to trauma. Am J Physiol. 1966 Jul;211(1):151–156. doi: 10.1152/ajplegacy.1966.211.1.151. [DOI] [PubMed] [Google Scholar]
  22. Parant M., Riveau G., Parant F., Dinarello C. A., Wolff S. M., Chedid L. Effect of indomethacin on increased resistance to bacterial infection and on febrile responses induced by muramyl dipeptide. J Infect Dis. 1980 Nov;142(5):708–715. doi: 10.1093/infdis/142.5.708. [DOI] [PubMed] [Google Scholar]
  23. Pekarek R. S., Beisel W. R. Characterization of the endogenous mediator(s) of serum zinc and iron depression during infection and other stresses. Proc Soc Exp Biol Med. 1971 Nov;138(2):728–732. doi: 10.3181/00379727-138-35977. [DOI] [PubMed] [Google Scholar]
  24. Powanda M. C., Beisel W. R. Hypothesis: leukocyte endogenous mediator/endogenous pyrogen/lymphocyte-activating factor modulates the development of nonspecific and specific immunity and affects nutritional status. Am J Clin Nutr. 1982 Apr;35(4):762–768. doi: 10.1093/ajcn/35.4.762. [DOI] [PubMed] [Google Scholar]
  25. Powanda M. C. Changes in body balances of nitrogen and other key nutrients: description and underlying mechanisms. Am J Clin Nutr. 1977 Aug;30(8):1254–1268. doi: 10.1093/ajcn/30.8.1254. [DOI] [PubMed] [Google Scholar]
  26. Rosenwasser L. J., Dinarello C. A., Rosenthal A. S. Adherent cell function in murine T-lymphocyte antigen recognition. IV. Enhancement of murine T-cell antigen recognition by human leukocytic pyrogen. J Exp Med. 1979 Sep 19;150(3):709–714. doi: 10.1084/jem.150.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sakamoto A., Moldawer L. L., Palombo J. D., Desai S. P., Bistrian B. R., Blackburn G. L. Alterations in tyrosine and protein kinetics produced by injury and branched chain amino acid administration in rats. Clin Sci (Lond) 1983 Mar;64(3):321–331. doi: 10.1042/cs0640321. [DOI] [PubMed] [Google Scholar]
  28. Sugarman B. Zinc and infection. Rev Infect Dis. 1983 Jan-Feb;5(1):137–147. doi: 10.1093/clinids/5.1.137. [DOI] [PubMed] [Google Scholar]
  29. Tocco R. J., Kahn L. L., Kluger M. J., Vander A. J. Relationship of trace metals to fever during infection: are prostaglandins involved? Am J Physiol. 1983 Mar;244(3):R368–R373. doi: 10.1152/ajpregu.1983.244.3.R368. [DOI] [PubMed] [Google Scholar]
  30. Wannemacher R. W., Jr, Pekarek R. S., Thompson W. L., Curnow R. T., Beall F. A., Zenser T. V., DeRubertis F. R., Beisel W. R. A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins. Endocrinology. 1975 Mar;96(3):651–661. doi: 10.1210/endo-96-3-651. [DOI] [PubMed] [Google Scholar]
  31. Yang R. D., Moldawer L. L., Sakamoto A., Keenan R. A., Matthews D. E., Young V. R., Wannemacher R. W., Jr, Blackburn G. L., Bistrian B. R. Leukocyte endogenous mediator alters protein dynamics in rats. Metabolism. 1983 Jul;32(7):654–660. doi: 10.1016/0026-0495(83)90120-8. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES