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. 1997 Mar;4(2):138–141. doi: 10.1128/cdli.4.2.138-141.1997

Depletion of endogenous interleukin-10 augments interleukin-1 beta secretion by Mycobacterium bovis BCG-reactive human cells.

P Méndez-Samperio 1, E Garcia-Martinez 1, M Hernandez-Garay 1, M Solis-Cardona 1
PMCID: PMC170492  PMID: 9067646

Abstract

In this study, we found evidence that the interleukin-10 (IL-10) protein is functionally relevant in Mycobacterium bovis BCG-induced cytokine synthesis, as neutralization of endogenously synthesized IL-10 in human cells activated with BCG resulted in a two- to threefold increase in the level of IL-1 beta. When exogenous recombinant human IL-10 was added to human mononuclear cells, a significant reduction of BCG-induced IL-1 beta secretion was observed. This inhibitory effect was not attributed to a cytotoxic effect, since trypan blue exclusion studies indicated no loss of cell viability in the presence of IL-10, and it was specific, as it was completely abolished in the presence of anti-IL-10 neutralizing monoclonal antibody while an irrelevant antibody used as a control had no effect. Taken together, these are the first studies that demonstrate that the depletion of endogenous IL-10 via anti-IL-10 antibody results in a very significantly enhanced BCG-induced IL-1 beta secretion and that the addition of exogenous IL-10 to human mononuclear cells stimulated with BCG inhibits IL-1 beta production. Further experimental work is needed to determine if the neutralization of IL-10 activity via anti-IL-10 antibody indeed enhances cytokine synthesis in vivo. However, the present results may be of importance, since the use of anti-IL-10 antibody could presumably contribute to the protective immunity induced by BCG against tuberculosis via an increase in cytokine synthesis that would amplify antimicrobial systems.

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Selected References

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  1. Barnes P. F., Abrams J. S., Lu S., Sieling P. A., Rea T. H., Modlin R. L. Patterns of cytokine production by mycobacterium-reactive human T-cell clones. Infect Immun. 1993 Jan;61(1):197–203. doi: 10.1128/iai.61.1.197-203.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes P. F., Chatterjee D., Abrams J. S., Lu S., Wang E., Yamamura M., Brennan P. J., Modlin R. L. Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J Immunol. 1992 Jul 15;149(2):541–547. [PubMed] [Google Scholar]
  3. Barnes P. F., Lu S., Abrams J. S., Wang E., Yamamura M., Modlin R. L. Cytokine production at the site of disease in human tuberculosis. Infect Immun. 1993 Aug;61(8):3482–3489. doi: 10.1128/iai.61.8.3482-3489.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Becker J. C., Czerny C., Bröcker E. B. Maintenance of clonal anergy by endogenously produced IL-10. Int Immunol. 1994 Oct;6(10):1605–1612. doi: 10.1093/intimm/6.10.1605. [DOI] [PubMed] [Google Scholar]
  5. Bermudez L. E., Champsi J. Infection with Mycobacterium avium induces production of interleukin-10 (IL-10), and administration of anti-IL-10 antibody is associated with enhanced resistance to infection in mice. Infect Immun. 1993 Jul;61(7):3093–3097. doi: 10.1128/iai.61.7.3093-3097.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bloom B. R., Murray C. J. Tuberculosis: commentary on a reemergent killer. Science. 1992 Aug 21;257(5073):1055–1064. doi: 10.1126/science.257.5073.1055. [DOI] [PubMed] [Google Scholar]
  7. Bogdan C., Vodovotz Y., Nathan C. Macrophage deactivation by interleukin 10. J Exp Med. 1991 Dec 1;174(6):1549–1555. doi: 10.1084/jem.174.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Boom W. H., Wallis R. S., Chervenak K. A. Human Mycobacterium tuberculosis-reactive CD4+ T-cell clones: heterogeneity in antigen recognition, cytokine production, and cytotoxicity for mononuclear phagocytes. Infect Immun. 1991 Aug;59(8):2737–2743. doi: 10.1128/iai.59.8.2737-2743.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chantry D., Turner M., Abney E., Feldmann M. Modulation of cytokine production by transforming growth factor-beta. J Immunol. 1989 Jun 15;142(12):4295–4300. [PubMed] [Google Scholar]
  10. Colditz G. A., Brewer T. F., Berkey C. S., Wilson M. E., Burdick E., Fineberg H. V., Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994 Mar 2;271(9):698–702. [PubMed] [Google Scholar]
  11. Dallman M. J., Shiho O., Page T. H., Wood K. J., Morris P. J. Peripheral tolerance to alloantigen results from altered regulation of the interleukin 2 pathway. J Exp Med. 1991 Jan 1;173(1):79–87. doi: 10.1084/jem.173.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dinarello C. A., Cannon J. G., Wolff S. M. New concepts on the pathogenesis of fever. Rev Infect Dis. 1988 Jan-Feb;10(1):168–189. doi: 10.1093/clinids/10.1.168. [DOI] [PubMed] [Google Scholar]
  13. Ding L., Linsley P. S., Huang L. Y., Germain R. N., Shevach E. M. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J Immunol. 1993 Aug 1;151(3):1224–1234. [PubMed] [Google Scholar]
  14. Ellner J. J., Hinman A. R., Dooley S. W., Fischl M. A., Sepkowitz K. A., Goldberger M. J., Shinnick T. M., Iseman M. D., Jacobs W. R., Jr Tuberculosis symposium: emerging problems and promise. J Infect Dis. 1993 Sep;168(3):537–551. doi: 10.1093/infdis/168.3.537. [DOI] [PubMed] [Google Scholar]
  15. Ellner J. J., Wallis R. S. Immunologic aspects of mycobacterial infections. Rev Infect Dis. 1989 Mar-Apr;11 (Suppl 2):S455–S459. doi: 10.1093/clinids/11.supplement_2.s455. [DOI] [PubMed] [Google Scholar]
  16. Gercken J., Pryjma J., Ernst M., Flad H. D. Defective antigen presentation by Mycobacterium tuberculosis-infected monocytes. Infect Immun. 1994 Aug;62(8):3472–3478. doi: 10.1128/iai.62.8.3472-3478.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johnson B. J., McMurray D. N. Cytokine gene expression by cultures of human lymphocytes with autologous Mycobacterium tuberculosis-infected monocytes. Infect Immun. 1994 Apr;62(4):1444–1450. doi: 10.1128/iai.62.4.1444-1450.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lowrie D. B. Is macrophage death on the field of battle essential to victory, or a tactical weakness in immunity against tuberculosis? Clin Exp Immunol. 1990 Jun;80(3):301–303. doi: 10.1111/j.1365-2249.1990.tb03285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mosmann T. R., Moore K. W. The role of IL-10 in crossregulation of TH1 and TH2 responses. Immunol Today. 1991 Mar;12(3):A49–A53. doi: 10.1016/S0167-5699(05)80015-5. [DOI] [PubMed] [Google Scholar]
  20. Méndez-Samperio P., Hernandez-Garay M., Badillo-Flores A., Nuñez-Vazquez A. Down-modulation of mycobacterial-induced IL-1 beta production in human mononuclear cells by IL-4. Clin Exp Immunol. 1996 May;104(2):374–379. doi: 10.1046/j.1365-2249.1996.06695.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ordway D. J., Sonnenberg M. G., Donahue S. A., Belisle J. T., Orme I. M. Drug-resistant strains of Mycobacterium tuberculosis exhibit a range of virulence for mice. Infect Immun. 1995 Feb;63(2):741–743. doi: 10.1128/iai.63.2.741-743.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oswald I. P., Gazzinelli R. T., Sher A., James S. L. IL-10 synergizes with IL-4 and transforming growth factor-beta to inhibit macrophage cytotoxic activity. J Immunol. 1992 Jun 1;148(11):3578–3582. [PubMed] [Google Scholar]
  23. Oswald I. P., Wynn T. A., Sher A., James S. L. Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8676–8680. doi: 10.1073/pnas.89.18.8676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Raviglione M. C., Snider D. E., Jr, Kochi A. Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide epidemic. JAMA. 1995 Jan 18;273(3):220–226. [PubMed] [Google Scholar]
  25. Sánchez F. O., Rodríguez J. I., Agudelo G., García L. F. Immune responsiveness and lymphokine production in patients with tuberculosis and healthy controls. Infect Immun. 1994 Dec;62(12):5673–5678. doi: 10.1128/iai.62.12.5673-5678.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thomssen H., Kahan M., Londei M. Differential effects of interleukin-10 on the expression of HLA class II and CD1 molecules induced by granulocyte/macrophage colony-stimulating factor/interleukin-4. Eur J Immunol. 1995 Sep;25(9):2465–2470. doi: 10.1002/eji.1830250909. [DOI] [PubMed] [Google Scholar]
  27. Toossi Z., Young T. G., Averill L. E., Hamilton B. D., Shiratsuchi H., Ellner J. J. Induction of transforming growth factor beta 1 by purified protein derivative of Mycobacterium tuberculosis. Infect Immun. 1995 Jan;63(1):224–228. doi: 10.1128/iai.63.1.224-228.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wallis R. S., Amir-Tahmasseb M., Ellner J. J. Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte western blot. Proc Natl Acad Sci U S A. 1990 May;87(9):3348–3352. doi: 10.1073/pnas.87.9.3348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Willems F., Marchant A., Delville J. P., Gérard C., Delvaux A., Velu T., de Boer M., Goldman M. Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol. 1994 Apr;24(4):1007–1009. doi: 10.1002/eji.1830240435. [DOI] [PubMed] [Google Scholar]
  30. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. de Waal Malefyt R., Haanen J., Spits H., Roncarolo M. G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., de Vries J. E. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. doi: 10.1084/jem.174.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]

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