Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1989 Mar;410:367–380. doi: 10.1113/jphysiol.1989.sp017538

Temperature and metabolic changes in rats after various doses of tumour necrosis factor alpha.

D C Bibby 1, R F Grimble 1
PMCID: PMC1190484  PMID: 2795483

Abstract

1. Sub-lethal doses of recombinant of tumour necrosis factor alpha (TNF alpha) were administered i.v. to young conscious male Wistar rats. Temperature changes and alterations in serum zinc and albumin concentrations and weight and composition of liver, kidney, spleen, tibialis muscle and skin were measured. Temperatures were monitored for 8 h and tissue parameters 8 and 22 h post-injection. 2. Doses above 10 micrograms/kg caused fevers of increasing magnitude and duration with latencies of 2 h. At doses of 200 micrograms/kg or more fevers were preceded by a fall in rectal temperature of up to 1.1 degrees C. 3. Weight loss by skin and tibialis and gain by liver occurred 22 h post-injection. Spleen and kidney weight and zinc and spleen protein contents were unaffected. Serum albumin and zinc fell 22 and 8 h after injection respectively. Liver zinc was elevated at both times and inversely correlated at 8 h with serum values. A degree of dose dependence of zinc and albumin changes existed. A gain in protein was evident in liver 8 h post-injection and a loss by muscle at 22 h. Paradoxical effects were observed in skin protein concentration. 4. TNF alpha mimicked many of the metabolic effects of E. coli endotoxin reported in the literature and showed similar effects to those described for interleukin 1 (IL1).

Full text

PDF
367

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. Metabolic effects of infection. Prog Food Nutr Sci. 1984;8(1-2):43–75. [PubMed] [Google Scholar]
  3. Beutler B. A., Milsark I. W., Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol. 1985 Dec;135(6):3972–3977. [PubMed] [Google Scholar]
  4. Beutler B., Mahoney J., Le Trang N., Pekala P., Cerami A. Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J Exp Med. 1985 May 1;161(5):984–995. doi: 10.1084/jem.161.5.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dayer J. M., Beutler B., Cerami A. Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med. 1985 Dec 1;162(6):2163–2168. doi: 10.1084/jem.162.6.2163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dinarello C. A. Multiple biological properties of recombinant human interleukin 1 (beta). Immunobiology. 1986 Sep;172(3-5):301–315. doi: 10.1016/S0171-2985(86)80112-7. [DOI] [PubMed] [Google Scholar]
  8. Feingold K. R., Grunfeld C. Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. J Clin Invest. 1987 Jul;80(1):184–190. doi: 10.1172/JCI113046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ford D. M., Klugman K. P. Body mass and sex as determining factors in the development of fever in rats. J Physiol. 1980 Jul;304:43–50. doi: 10.1113/jphysiol.1980.sp013308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gifford G. E., Flick D. A. Natural production and release of tumour necrosis factor. Ciba Found Symp. 1987;131:3–20. doi: 10.1002/9780470513521.ch2. [DOI] [PubMed] [Google Scholar]
  11. Jepson M. M., Pell J. M., Bates P. C., Millward D. J. The effects of endotoxaemia on protein metabolism in skeletal muscle and liver of fed and fasted rats. Biochem J. 1986 Apr 15;235(2):329–336. doi: 10.1042/bj2350329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kettelhut I. C., Fiers W., Goldberg A. L. The toxic effects of tumor necrosis factor in vivo and their prevention by cyclooxygenase inhibitors. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4273–4277. doi: 10.1073/pnas.84.12.4273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Lang C. H., Bagby G. J., Spitzer J. J. Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin. Am J Physiol. 1985 Apr;248(4 Pt 2):R471–R478. doi: 10.1152/ajpregu.1985.248.4.R471. [DOI] [PubMed] [Google Scholar]
  15. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  16. McPherson I. G., Everard D. W. Serum albumin estimation: modification of the bromcresol green method. Clin Chim Acta. 1972 Mar;37:117–121. doi: 10.1016/0009-8981(72)90422-6. [DOI] [PubMed] [Google Scholar]
  17. Perlmutter D. H., Dinarello C. A., Punsal P. I., Colten H. R. Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest. 1986 Nov;78(5):1349–1354. doi: 10.1172/JCI112721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Scuderi P., Sterling K. E., Lam K. S., Finley P. R., Ryan K. J., Ray C. G., Petersen E., Slymen D. J., Salmon S. E. Raised serum levels of tumour necrosis factor in parasitic infections. Lancet. 1986 Dec 13;2(8520):1364–1365. doi: 10.1016/s0140-6736(86)92007-6. [DOI] [PubMed] [Google Scholar]
  19. Shoham S., Davenne D., Cady A. B., Dinarello C. A., Krueger J. M. Recombinant tumor necrosis factor and interleukin 1 enhance slow-wave sleep. Am J Physiol. 1987 Jul;253(1 Pt 2):R142–R149. doi: 10.1152/ajpregu.1987.253.1.R142. [DOI] [PubMed] [Google Scholar]
  20. Stashenko P., Dewhirst F. E., Peros W. J., Kent R. L., Ago J. M. Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J Immunol. 1987 Mar 1;138(5):1464–1468. [PubMed] [Google Scholar]
  21. Stitt J. T., Shimada S. G. A comparison of the febrile responses of the Brattleboro and Sprague-Dawley strains of rats to endotoxin and endogenous pyrogens. Can J Physiol Pharmacol. 1987 Jun;65(6):1377–1381. doi: 10.1139/y87-216. [DOI] [PubMed] [Google Scholar]
  22. Tocco-Bradley R., Kluger M. J. Zinc concentration and survival in rats infected with Salmonella typhimurium. Infect Immun. 1984 Aug;45(2):332–338. doi: 10.1128/iai.45.2.332-338.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  24. Waage A. Production and clearance of tumor necrosis factor in rats exposed to endotoxin and dexamethasone. Clin Immunol Immunopathol. 1987 Dec;45(3):348–355. doi: 10.1016/0090-1229(87)90087-0. [DOI] [PubMed] [Google Scholar]
  25. Warren R. S., Starnes H. F., Jr, Gabrilove J. L., Oettgen H. F., Brennan M. F. The acute metabolic effects of tumor necrosis factor administration in humans. Arch Surg. 1987 Dec;122(12):1396–1400. doi: 10.1001/archsurg.1987.01400240042007. [DOI] [PubMed] [Google Scholar]
  26. Williams D. A. A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics. 1971 Mar;27(1):103–117. [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES