Increased production of interleukin-10 by human blood monocytes stimulated with Mycobacterium avium-intracellulare...

Macrophages produce various cytokines in response to mycobacteria, including interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha). IL-10 has been shown to down-regulate numerous macrophage functions, including microbicidal activity against intracellular bacteria and parasites. IL-10 also inhibits interferon-gamma (IFN-gamma) production and antigen-specific proliferation of Th1 cells mediating immunologic resistance to mycobacterial infection. In contrast, TNF-alpha activates macrophages and may augment their mycobacterial activity. In this study, peripheral blood mononuclear cells (PBMC) or blood monocytes obtained from healthy tuberculin reactors were stimulated in vitro with heat-killed Mycobacterium tuberculosis or heat-killed M. avium-intracellulare complex (MAC) to produce IL-10 and TNF-alpha. We studied a total of 26 clinical isolates of M. tuberculosis and 28 isolates of MAC. MAC-stimulated PBMC and monocytes released significantly larger amounts of IL-10 than those cells stimulated with M. tuberculosis. However, there was no difference in induction of TNF-alpha production between MAC and M. tuberculosis. When TNF-activity was neutralized by the addition of anti-TNF-alpha mAb in culture, MAC still induced more IL-10 secretion than did M. tuberculosis. These findings suggest that increased production of IL-10 by MAC-stimulated monocytes may play a role in the intractable disease caused by these organisms.