The modulating effects of proinflammatory cytokines interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), and immunoregulating cytokines IL-10 and transforming growth factor-beta (TGF-β), on anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex

Abstract

SUMMARY We assessed the roles of proinflammatory cytokines IFN-γ and TNF-α, and immunoregulatory cytokines IL-10 and TGF-β in the modulation of the anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex (MAIC). First, both IFN-γ and TNF-α significantly reduced the bacterial growth in macrophages, indicating that these cytokines participate in up-regulation of macrophage anti-MAIC function. Second, although MAIC-infected macrophages produced substantial amounts of IL-10 and TGF-β, neutralization of endogenous IL-10 and TGF-β with anti-IL-10 and anti-TGF-β antibodies, respectively, did not affect the intracellular growth of MAIC in macrophages from mice with BcgS (MAIC-susceptible) or Bcgr (MAIC-resistant) genotype, regardless of the virulence of test MAIC strains. The same result was also obtained for macrophages stimulated with IFN-γ or TNF-α. Third, in MAIC-infected mice, the growth of organisms at the sites of infection (lungs and spleens) was not affected by administration of anti-IL-10 or anti-TGF-β antibodies. These findings indicate that, in the case of mice, endogenous IL-10 and TGF-β are essentially ineffective in down-regulating macrophage anti-MAIC functions not only in vitro but also in vivo.