Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1983 Jun;40(3):1011–1014. doi: 10.1128/iai.40.3.1011-1014.1983

Steroids inhibit activation of the alternative-amplification pathway of complement.

B D Packard, J M Weiler
PMCID: PMC348151  PMID: 6343236

Abstract

Previous studies have demonstrated the ability of methylprednisolone sodium succinate to inhibit complement activation. Two other glucocorticosteroids and three different soluble steroids which lacked glucocorticoid activity were found in the present study to have the capacity to inhibit lysis of sheep erythrocytes by the alternative-amplification pathway. These compounds also inhibited fluid-phase consumption of B in a reaction mixture that contained purified C3b, B, and D, indicating that they exert a direct effect on the generation of alternative amplification pathway convertase. These findings suggest that the capacity to inhibit convertase generation by glucocorticosteroids in high concentration is independent of glucocorticoid activity.

Full text

PDF
1011

Selected References

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

  1. Dessypris A. G. Testosterone sulphate, its biosynthesis, metabolism, measurement, functions and properties. J Steroid Biochem. 1975 Aug;6(8):1287–1298. doi: 10.1016/0022-4731(75)90120-x. [DOI] [PubMed] [Google Scholar]
  2. Fauci A. S., Dale D. C., Balow J. E. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med. 1976 Mar;84(3):304–315. doi: 10.7326/0003-4819-84-3-304. [DOI] [PubMed] [Google Scholar]
  3. Fearon D. T., Austen K. F. Activation of the alternative complement pathway due to resistance of zymosan-bound amplification convertase to endogenous regulatory mechanisms. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1683–1687. doi: 10.1073/pnas.74.4.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fearon D. T., Austen K. F. Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins. J Exp Med. 1977 Jul 1;146(1):22–33. doi: 10.1084/jem.146.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fearon D. T., Austen K. F. Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. J Exp Med. 1975 Oct 1;142(4):856–863. doi: 10.1084/jem.142.4.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fearon D. T., Austen K. F. Properdin: initiation of alternative complement pathway. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3220–3224. doi: 10.1073/pnas.72.8.3220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fearon D. T., Austen K. F., Ruddy S. Formation of a hemolytically active cellular intermediate by the interaction between properdin factors B and D and the activated third component of complement. J Exp Med. 1973 Dec 1;138(6):1305–1313. doi: 10.1084/jem.138.6.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gewurz H., Wernick P. R., Quie P. G., Good R. A. Effects of hydrocortisone succinate on the complement system. Nature. 1965 Nov 20;208(5012):755–757. doi: 10.1038/208755a0. [DOI] [PubMed] [Google Scholar]
  9. Gitlin J. D., Rosen F. S., Lachmann P. J. The mechanism of action of the C3b inactivator (conglutinogen-activating factor) on its naturally occurring substrate, the major fragment of the third component of complement (C3b). J Exp Med. 1975 May 1;141(5):1221–1226. doi: 10.1084/jem.141.5.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hammerschmidt D. E., White J. G., Craddock P. R., Jacob H. S. Corticosteroids inhibit complement-induced granulocyte aggregation. A possible mechanism for their efficacy in shock states. J Clin Invest. 1979 Apr;63(4):798–803. doi: 10.1172/JCI109365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hinshaw L. B., Archer L. T., Beller-Todd B. K., Coalson J. J., Flournoy D. J., Passey R., Benjamin B., White G. L. Survival of primates in LD100 septic shock following steroid/antibiotic therapy. J Surg Res. 1980 Feb;28(2):151–170. doi: 10.1016/0022-4804(80)90158-4. [DOI] [PubMed] [Google Scholar]
  12. Hunsicker L. G., Ruddy S., Austen K. F. Alternate complement pathway: factors involved in cobra venom factor (CoVF) activation of the third component of complement (C3). J Immunol. 1973 Jan;110(1):128–138. [PubMed] [Google Scholar]
  13. JENNINGS J. F., TAYLOR G. EFFECT OF HYDROCORTISONE HEMI-SUCCINATE ON IMMUNE LYSIS OF SHEEP ERYTHROCYTES. Nature. 1964 Aug 8;203:661–661. doi: 10.1038/203661a0. [DOI] [PubMed] [Google Scholar]
  14. Jacob H. S. Complement-induced vascular leukostasis. Its role in tissue injury. Arch Pathol Lab Med. 1980 Dec;104(12):617–620. [PubMed] [Google Scholar]
  15. Jacob H. S., Craddock P. R., Hammerschmidt D. E., Moldow C. F. Complement-induced granulocyte aggregation: an unsuspected mechanism of disease. N Engl J Med. 1980 Apr 3;302(14):789–794. doi: 10.1056/NEJM198004033021407. [DOI] [PubMed] [Google Scholar]
  16. Parrillo J. E., Fauci A. S. Mechanisms of glucocorticoid action on immune processes. Annu Rev Pharmacol Toxicol. 1979;19:179–201. doi: 10.1146/annurev.pa.19.040179.001143. [DOI] [PubMed] [Google Scholar]
  17. Schumer W. Steroids in the treatment of clinical septic shock. Ann Surg. 1976 Sep;184(3):333–341. doi: 10.1097/00000658-197609000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sladen A. Methylprednisolone. Pharmacologic doses in shock lung syndrome. J Thorac Cardiovasc Surg. 1976 May;71(5):800–806. [PubMed] [Google Scholar]
  19. Tack B. D., Prahl J. W. Third component of human complement: purification from plasma and physicochemical characterization. Biochemistry. 1976 Oct 5;15(20):4513–4521. doi: 10.1021/bi00665a028. [DOI] [PubMed] [Google Scholar]
  20. Weiler J. M., Packard B. D. Methylprednisolone inhibits the alternative and amplification pathways of complement. Infect Immun. 1982 Oct;38(1):122–126. doi: 10.1128/iai.38.1.122-126.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Weiler J. M., Yurt R. W., Fearon D. T., Austen K. F. Modulation of the formation of the amplification convertase of complement, C3b, Bb, by native and commercial heparin. J Exp Med. 1978 Feb 1;147(2):409–421. doi: 10.1084/jem.147.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES