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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1986 Aug;65(2):279–285.

Decreased interleukin 2 inhibitor in sera of patients with autoimmune disorders.

J Y Djeu, T Kasahara, J E Balow, G C Tsokos
PMCID: PMC1542294  PMID: 3791699

Abstract

The lymphokine, interleukin 2 (IL-2), is an important modulator of cell-mediated immune (CMI) responses. We report here the detection of an inhibitor of IL-2 in normal sera by measuring the inhibition of thymidine incorporation in IL-2 dependent murine CTLL cells. The inhibitor, partially purified by Sephacryl S-200 gel filtration, eluted with the 60,000-70,000 mol. wt fraction. The factor was destroyed at 56 degrees C for 30 min and did not bind to Protein A Sepharose, suggesting that it is not an immunoglobulin G. Of 26 normal sera tested, 23 had significant levels of the inhibitor. Since connective tissue diseases are often associated with deficient CMI responses, we examined the levels of IL-2 inhibitor in 26 systemic lupus erythematosus (SLE) and 22 rheumatoid arthritis (RA) patients. Only 8 SLE and 12 RA patients had normal levels of the inhibitor. Of the 18 SLE patients with low or undetectable levels, 15 had clinically defined active disease and of the eight with normal levels, three had active disease. The decrease in the IL-2 inhibitor level did not correlate either with steroid or cyclophosphamide treatment or with serum levels of DNA binding and C3. These data suggest that the function of the inhibitor is to control IL-2 activity under normal conditions. Decreased levels of the IL-2 inhibitor in these patients might be explained either as a reduced requirement of this regulatory protein secondary to decreased IL-2 production or a defect of the cells responsible for the production of both IL-2 and its inhibitor.

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Selected References

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

  1. Farrar J. J., Benjamin W. R., Hilfiker M. L., Howard M., Farrar W. L., Fuller-Farrar J. The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic T cell and antibody-forming B cell responses. Immunol Rev. 1982;63:129–166. doi: 10.1111/j.1600-065x.1982.tb00414.x. [DOI] [PubMed] [Google Scholar]
  2. Hardt C., Röllinghoff M., Pfizenmaier K., Mosmann H., Wagner H. Lyt-23+ cyclophosphamide-sensitive T cells regulate the activity of an interleukin 2 inhibitor in vivo. J Exp Med. 1981 Aug 1;154(2):262–274. doi: 10.1084/jem.154.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Henney C. S., Kuribayashi K., Kern D. E., Gillis S. Interleukin-2 augments natural killer cell activity. Nature. 1981 May 28;291(5813):335–338. doi: 10.1038/291335a0. [DOI] [PubMed] [Google Scholar]
  4. Honda M., Chan C., Shevach E. M. Characterization and partial purification of a specific interleukin 2 inhibitor. J Immunol. 1985 Sep;135(3):1834–1839. [PubMed] [Google Scholar]
  5. Itoh K., Tilden A. B., Balch C. M. Role of interleukin 2 and a serum suppressive factor on the induction of activated killer cells cytotoxic for autologous human melanoma cells. Cancer Res. 1985 Jul;45(7):3173–3178. [PubMed] [Google Scholar]
  6. Lelchuk R., Playfair J. H. Serum IL-2 inhibitor in mice. I. Increase during infection. Immunology. 1985 Sep;56(1):113–118. [PMC free article] [PubMed] [Google Scholar]
  7. Linker-Israeli M., Bakke A. C., Quismorio F. P., Jr, Horwitz D. A. Correction of interleukin-2 production in patients with systemic lupus erythematosus by removal of spontaneously activated suppressor cells. J Clin Invest. 1985 Feb;75(2):762–768. doi: 10.1172/JCI111758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lotze M. T., Frana L. W., Sharrow S. O., Robb R. J., Rosenberg S. A. In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of the Jurkat cell line-derived interleukin 2. J Immunol. 1985 Jan;134(1):157–166. [PubMed] [Google Scholar]
  9. Luger T. A., Smolen J. S., Chused T. M., Steinberg A. D., Oppenheim J. J. Human lymphocytes with either the OKT4 or OKT8 phenotype produce interleukin 2 in culture. J Clin Invest. 1982 Aug;70(2):470–473. doi: 10.1172/JCI110637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Male D., Lelchuk R., Curry S., Pryce G., Playfair J. H. Serum IL-2 inhibitor in mice. II. Molecular characteristics. Immunology. 1985 Sep;56(1):119–125. [PMC free article] [PubMed] [Google Scholar]
  11. Nicholas N. S., Panayi G. S. Inhibition of interleukin-2 production by retroplacental sera: a possible mechanism for human fetal allograft survival. Am J Reprod Immunol Microbiol. 1985 Sep;9(1):6–11. doi: 10.1111/j.1600-0897.1985.tb00332.x. [DOI] [PubMed] [Google Scholar]
  12. Nicholas N. S., Panayi G. S., Nouri A. M. Human pregnancy serum inhibits interleukin-2 production. Clin Exp Immunol. 1984 Dec;58(3):587–595. [PMC free article] [PubMed] [Google Scholar]
  13. Rook A. H., Masur H., Lane H. C., Frederick W., Kasahara T., Macher A. M., Djeu J. Y., Manischewitz J. F., Jackson L., Fauci A. S. Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome. J Clin Invest. 1983 Jul;72(1):398–403. doi: 10.1172/JCI110981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Siegel J. P., Djeu J. Y., Stocks N. I., Masur H., Gelmann E. P., Quinnan G. V., Jr Sera from patients with the acquired immunodeficiency syndrome inhibit production of interleukin-2 by normal lymphocytes. J Clin Invest. 1985 Jun;75(6):1957–1964. doi: 10.1172/JCI111912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stadler B. M., Berenstein E. H., Siraganian R. P., Oppenheim J. J. Monoclonal antibody against human interleukin 2 (IL 2). I. Purification of IL 2 for the production of monoclonal antibodies. J Immunol. 1982 Apr;128(4):1620–1624. [PubMed] [Google Scholar]
  16. Stadler B. M., Dougherty S. F., Farrar J. J., Oppenheim J. J. Relationship of cell cycle to recovery of IL 2 activity from human mononuclear cells, human and mouse T cell lines. J Immunol. 1981 Nov;127(5):1936–1940. [PubMed] [Google Scholar]
  17. Tsokos G. C., Balow J. E. Cellular immune responses in systemic lupus erythematosus. Prog Allergy. 1984;35:93–161. [PubMed] [Google Scholar]
  18. Tsokos G. C., Smith P. L., Christian C. B., Lipnick R. N., Balow J. E., Djeu J. Y. Interleukin-2 restores the depressed allogeneic cell-mediated lympholysis and natural killer cell activity in patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1985 Mar;34(3):379–386. doi: 10.1016/0090-1229(85)90186-2. [DOI] [PubMed] [Google Scholar]
  19. Wolf R. L., Andreoni J. Soluble inhibitory factor (SIF) in normal human serum. Cell Immunol. 1982 Mar 1;67(2):299–311. doi: 10.1016/0008-8749(82)90222-2. [DOI] [PubMed] [Google Scholar]

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