Dual role of interleukin-10 in murine lyme disease: Regulation of arthritis severity and host defense

In the murine model of Lyme disease, C3H/He mice exhibit severe arthritis w hile C57BL/6N mice exhibit mild lesions when infected with Borrelia burgdor feri. Joint tissues from these two strains of mice harbor similar concentra tions of B. burgdorferi, suggesting that the difference in disease severity reflects differences in the magnitude of the inflammatory response to B. b urgdorferi lipoproteins. Stimulation of bone marrow macrophages from C3H/He N mice with the B. burgdorferi lipoprotein OspA resulted in higher-level pr oduction of the inflammatory mediators tumor necrosis factor alpha, nitric oxide, and interleukin-6 (IL-6) than that of macrophages from C57BL/6N mice . In contrast, macrophages from C57BL/6N mice consistently produced larger amounts of the anti-inflammatory cytokine IL-10 than did C3H/HeN macrophage s. Addition of recombinant IL-10 suppressed the production of inflammatory mediators by macrophages from both strains. IL-10 was found to modulate B. burgdorferi-induced inflammation in vivo, since C57BL/6J mite deficient in IL-10 (IL-10(-/-)) developed more severe arthritis than wild-type C57BL/6J mice. The increase in arthritis severity was associated with a 10-fold decr ease in the number of B. burgdorferi organisms present in ankle tissues fro m IL-10(-/-) mice. These findings suggest that in C57BL/6 mice, IL-10-depen dent regulation of arthritis severity occurs at the expense of effective co ntrol of bacterial numbers.