Endogenous inhibition of antimycobacterial immunity by IL-10 varies between mycobacterial species

Interleukin (IL)-10 is an immunoregulatory cytokine that inhibits both Th1- like T cell responses and macrophage activation. Deficiency of IL-10 has be en associated with increased Th1-like CD4(+) T-cell responses and increased clearance of some intracellular pathogens, however, its role in mycobacter ial infections is controversial. In order to examine the effects of mycobac terial virulence on the outcome of infection we compared infection with Myc obacterium avium and virulent Mycobacterium tuberculosis in C57BI/6 IL-10(- /-) mice. M. avium infection in IL-10(-/-) mice resulted in sustained incre ases in interferon (IFN)-gamma -secreting T-cell responses and was associat ed with the increased clearance of M. avium from the liver and lung. By con trast, M. tuberculosis infection in IL-10(-/-) mice led to a transient incr ease in IFN-gamma T-cell responses at 4 weeks postinfection, with reduced b acterial burden in the lungs. This was not sustained so that by 8 weeks the re was no difference to wild-type (WT) mice. In vitro infection of IL-10(-/ -) macrophages with M. avium, but not M. tuberculosis, led to an increased IL-12 production. Therefore, endogenous IL-10 exerts a significant inhibiti on on specific IFN-gamma T-cell responses to M. avium infection, however, t his effect is short lived during the M. tuberculosis infection, and fails t o influence the long-term course of infection.