Increased antimycobacterial immunity in interleukin-10-deficient mice

Macrophage effector functions are essential for clearing mycobacterial infe ctions. Interleukin 10 (IL-10) negatively regulates macrophages and could b e a factor inhibiting effective antimycobacterial immunity. We previously s howed that transgenic mice which produce excess IL-10 from T cells are susc eptible to infection, even though these mice continue to produce gamma inte rferon (IFN-gamma) at levels similar to those in controls. Here, we extend our genetic analysis of the functions of IL-10 in antimycobacterial immunit y by testing the hypothesis that IL-10-deficient (IL-10(-/-)) mice should b e more resistant to mycobacteria than control mice. Mycobacterium bovis bac illus Calmette-Guerin-infected IL-10(-/-) mice had significantly lower bact erial burdens than control mice early in the infection. Contrary to expecta tions, however, IL-10-/- mice did not have increased levels of IFN-gamma, e ither from T cells or in the plasma, suggesting that other mechanisms are r esponsible for the increased resistance. However, macrophages From IL-10(-/ -) mice produced increased levels of inflammatory cytokines, including IFN- gamma, as well as nitric oxide and prostaglandins, which could account for increased antimycobacterial immunity. Our genetic analysis revealed that IL -10 is an inhibitor of early mycobacterial clearance. The data also suggest that IL-10 negatively regulates numerous macrophage functions as well as p laying a role in down-regulating the general inflammatory response, especia lly in conditions where an infection must be controlled through macrophage activity.