PRODUCTION OF TNF-ALPHA, IL-6 AND TGF-BETA, AND EXPRESSION OF RECEPTORS FOR TNF-ALPHA AND IL-6, DURING MURINE MYCOBACTERIUM-AVIUM INFECTION

The Mycobacterium avium complex comprises intracellular bacteria assoc iated with disseminated infection in patients with acquired immune def iciency syndrome (AIDS). Immune defects that lead to infection are unk nown but cytokines appear to play an important role in the immunomodul ation of host defence mechanisms. We evaluated the cytokine profiles s een temporally after murine M. avium infection. Spleen cells were obta ined from M. avium-infected C57BL/6 mice and uninfected mice at weeks 1, 2, 3, 4 and 5. Cells were cultured in vitro and subsequently pulsed with killed M. avium. Supernatants were collected from the cultured s plenic cells and the concentrations of interleukin-6 (IL-6), transform ing growth factor-beta(1) (TGF-beta(1)) and tumour necrosis factor-alp ha (TNF-alpha) were measured. TGF-beta(1) was detected at week 1, foll owed by IL-6 production at week 2. Elevated TNF-alpha levels were obse rved at week 3. The addition of polyclonal anti-TGF-beta(1) antibody t o M. avium-infected peritoneal macrophages in the presence of splenic cell supernatants from weeks 1, 3 and 5 led to decreased bacterial cou nts compared to controls, Anti-IL-6 antibody did not have any effect o n macrophage anti-mycobacterial activity. Concurrently, we observed de creased expression of TNF-alpha receptors on infected macrophages. We propose that the early elevated levels of TCF-beta(1), a known suppres sor of macrophage function, in conjunction with down-regulation of TNF -alpha receptors may help explain the suboptimal macrophage response t o TNF-alpha, leading to impaired anti-mycobacterial activity.