Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1992 Sep;216(3):381–387. doi: 10.1097/00000658-199209000-00018

Muscle protein breakdown during endotoxemia in rats and after treatment with interleukin-1 receptor antagonist (IL-1ra).

O Zamir 1, P O Hasselgren 1, W O'Brien 1, R C Thompson 1, J E Fischer 1
PMCID: PMC1242630  PMID: 1417187

Abstract

The purpose of this study was to examine the effect of endotoxemia on muscle protein degradation and to test the hypothesis that muscle proteolysis during endotoxemia is regulated by interleukin-1 (IL-1). Both total and myofibrillar protein breakdown rates in incubated extensor digitorum longus muscles were increased after the subcutaneous injection of 0.1 or 1.0 mg/kg endotoxin in rats. The endotoxin-induced increase in muscle protein breakdown was blunted by IL-1 receptor antagonist, administered intraperitoneally at a total dose of 45 or 105 mg/kg. Results suggest that endotoxemia in rats gives rise to sepsislike changes in muscle protein breakdown. Increased muscle protein breakdown during endotoxemia may be regulated, at least in part, by IL-1.

Full text

PDF
381

Selected References

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

  1. Alexander H. R., Doherty G. M., Buresh C. M., Venzon D. J., Norton J. A. A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice. J Exp Med. 1991 Apr 1;173(4):1029–1032. doi: 10.1084/jem.173.4.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arend W. P., Welgus H. G., Thompson R. C., Eisenberg S. P. Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist. J Clin Invest. 1990 May;85(5):1694–1697. doi: 10.1172/JCI114622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bates P. C., Millward D. J. Myofibrillar protein turnover. Synthesis rates of myofibrillar and sarcoplasmic protein fractions in different muscles and the changes observed during postnatal development and in response to feeding and starvation. Biochem J. 1983 Aug 15;214(2):587–592. doi: 10.1042/bj2140587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chizzonite R., Truitt T., Kilian P. L., Stern A. S., Nunes P., Parker K. P., Kaffka K. L., Chua A. O., Lugg D. K., Gubler U. Two high-affinity interleukin 1 receptors represent separate gene products. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8029–8033. doi: 10.1073/pnas.86.20.8029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clowes G. H., Jr, George B. C., Villee C. A., Jr, Saravis C. A. Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma. N Engl J Med. 1983 Mar 10;308(10):545–552. doi: 10.1056/NEJM198303103081001. [DOI] [PubMed] [Google Scholar]
  7. Dinarello C. A., Thompson R. C. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today. 1991 Nov;12(11):404–410. doi: 10.1016/0167-5699(91)90142-G. [DOI] [PubMed] [Google Scholar]
  8. Dower S. K., Kronheim S. R., March C. J., Conlon P. J., Hopp T. P., Gillis S., Urdal D. L. Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med. 1985 Aug 1;162(2):501–515. doi: 10.1084/jem.162.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dripps D. J., Brandhuber B. J., Thompson R. C., Eisenberg S. P. Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. J Biol Chem. 1991 Jun 5;266(16):10331–10336. [PubMed] [Google Scholar]
  10. Dripps D. J., Verderber E., Ng R. K., Thompson R. C., Eisenberg S. P. Interleukin-1 receptor antagonist binds to the type II interleukin-1 receptor on B cells and neutrophils. J Biol Chem. 1991 Oct 25;266(30):20311–20315. [PubMed] [Google Scholar]
  11. Eisenberg S. P., Evans R. J., Arend W. P., Verderber E., Brewer M. T., Hannum C. H., Thompson R. C. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990 Jan 25;343(6256):341–346. doi: 10.1038/343341a0. [DOI] [PubMed] [Google Scholar]
  12. Goldberg A. L., Kettelhut I. C., Furuno K., Fagan J. M., Baracos V. Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines. J Clin Invest. 1988 May;81(5):1378–1383. doi: 10.1172/JCI113466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldberg A. L., Martel S. B., Kushmerick M. J. In vitro preparations of the diaphragm and other skeletal muscles. Methods Enzymol. 1975;39:82–94. doi: 10.1016/s0076-6879(75)39012-5. [DOI] [PubMed] [Google Scholar]
  14. Hall-Angerås M., Angerås U., Hasselgren P. O., Fischer J. E. Effects of elevated temperature on protein breakdown in muscles from septic rats. Am J Physiol. 1990 Apr;258(4 Pt 1):C589–C592. doi: 10.1152/ajpcell.1990.258.4.C589. [DOI] [PubMed] [Google Scholar]
  15. Hall-Angerås M., Angerås U., Zamir O., Hasselgren P. O., Fischer J. E. Interaction between corticosterone and tumor necrosis factor stimulated protein breakdown in rat skeletal muscle, similar to sepsis. Surgery. 1990 Aug;108(2):460–466. [PubMed] [Google Scholar]
  16. Hall-Angerås M., Angerås U., von Allmen D., Higashiguchi T., Zamir O., Hasselgren P. O., Fischer J. E. Influence of sepsis in rats on muscle protein turnover in vivo and in tissue incubated under different in vitro conditions. Metabolism. 1991 Mar;40(3):247–251. doi: 10.1016/0026-0495(91)90105-6. [DOI] [PubMed] [Google Scholar]
  17. Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
  18. Hasselgren P. O., Hall-Angerås M., Angerås U., Benson D., James J. H., Fischer J. E. Regulation of total and myofibrillar protein breakdown in rat extensor digitorum longus and soleus muscle incubated flaccid or at resting length. Biochem J. 1990 Apr 1;267(1):37–44. doi: 10.1042/bj2670037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hasselgren P. O., James J. H., Benson D. W., Hall-Angerås M., Angerås U., Hiyama D. T., Li S., Fischer J. E. Total and myofibrillar protein breakdown in different types of rat skeletal muscle: effects of sepsis and regulation by insulin. Metabolism. 1989 Jul;38(7):634–640. doi: 10.1016/0026-0495(89)90100-5. [DOI] [PubMed] [Google Scholar]
  20. Hasselgren P. O., James J. H., Benson D. W., Li S., Fischer J. E. Is there a circulating proteolysis-inducing factor during sepsis? Arch Surg. 1990 Apr;125(4):510–514. doi: 10.1001/archsurg.1990.01410160096020. [DOI] [PubMed] [Google Scholar]
  21. Hasselgren P. O., Talamini M., James J. H., Fischer J. E. Protein metabolism in different types of skeletal muscle during early and late sepsis in rats. Arch Surg. 1986 Aug;121(8):918–923. doi: 10.1001/archsurg.1986.01400080064011. [DOI] [PubMed] [Google Scholar]
  22. Hummel R. P., 3rd, Hasselgren P. O., James J. H., Warner B. W., Fischer J. E. The effect of sepsis in rats on skeletal muscle protein synthesis in vivo and in periphery and central core of incubated muscle preparations in vitro. Metabolism. 1988 Dec;37(12):1120–1127. doi: 10.1016/0026-0495(88)90187-4. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. McIntyre K. W., Stepan G. J., Kolinsky K. D., Benjamin W. R., Plocinski J. M., Kaffka K. L., Campen C. A., Chizzonite R. A., Kilian P. L. Inhibition of interleukin 1 (IL-1) binding and bioactivity in vitro and modulation of acute inflammation in vivo by IL-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody. J Exp Med. 1991 Apr 1;173(4):931–939. doi: 10.1084/jem.173.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McMahan C. J., Slack J. L., Mosley B., Cosman D., Lupton S. D., Brunton L. L., Grubin C. E., Wignall J. M., Jenkins N. A., Brannan C. I. A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J. 1991 Oct;10(10):2821–2832. doi: 10.1002/j.1460-2075.1991.tb07831.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mealy K., van Lanschot J. J., Robinson B. G., Rounds J., Wilmore D. W. Are the catabolic effects of tumor necrosis factor mediated by glucocorticoids? Arch Surg. 1990 Jan;125(1):42–48. doi: 10.1001/archsurg.1990.01410130044006. [DOI] [PubMed] [Google Scholar]
  27. Ohlsson K., Björk P., Bergenfeldt M., Hageman R., Thompson R. C. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990 Dec 6;348(6301):550–552. doi: 10.1038/348550a0. [DOI] [PubMed] [Google Scholar]
  28. Ulich T. R., Yin S. M., Guo K. Z., del Castillo J., Eisenberg S. P., Thompson R. C. The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation. Am J Pathol. 1991 Mar;138(3):521–524. [PMC free article] [PubMed] [Google Scholar]
  29. Wakabayashi G., Gelfand J. A., Burke J. F., Thompson R. C., Dinarello C. A. A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits. FASEB J. 1991 Mar 1;5(3):338–343. doi: 10.1096/fasebj.5.3.1825816. [DOI] [PubMed] [Google Scholar]
  30. Warner B. W., Hasselgren P. O., James J. H., Hummel R. P., 3rd, Rigel D. F., Fischer J. E. Reduced amino acid transport in skeletal muscle caused by a circulating factor during endotoxemia. Ann Surg. 1990 Mar;211(3):323–328. doi: 10.1097/00000658-199003000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zamir O., Hasselgren P. O., Kunkel S. L., Frederick J., Higashiguchi T., Fischer J. E. Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis. Arch Surg. 1992 Feb;127(2):170–174. doi: 10.1001/archsurg.1992.01420020052008. [DOI] [PubMed] [Google Scholar]
  32. Zamir O., Hasselgren P. O., von Allmen D., Fischer J. E. The effect of interleukin-1 alpha and the glucocorticoid receptor blocker RU 38486 on total and myofibrillar protein breakdown in skeletal muscle. J Surg Res. 1991 Jun;50(6):579–583. doi: 10.1016/0022-4804(91)90045-n. [DOI] [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES