Gestational attenuation of Lyme arthritis is mediated by progesterone and IL-4

Infection of different strains of laboratory mice with the agent of Lyme di sease, Borrelia burgdorferi, results in arthritis, the severity of which ha s been correlated with the dominance of Th1 cytokines. In this study, we de monstrate that changes in B. burgdorferi-specific immunologic responses ass ociated with pregnancy can alter the outcome of Lyme arthritis in mice. Whe reas nonpregnant female C3H mice consistently developed severe Lyme arthrit is, pregnant mice had a marked reduction in arthritis severity that was ass ociated with a slight reduction in IFN-gamma and markedly increased levels of IL-4 production by B. burgdorferi-specific T cells. Similar reductions i n arthritis severity and patterns of cytokine production were observed in n onpregnant, progesterone-implanted mice. Ab neutralization of IL-4 in proge sterone-implanted mice resulted in severe arthritis. Our results are consis tent with the known shift toward Th2 cytokine expression at the maternal-fe tal interface, and are the first to show a pregnancy-related therapeutic ef fect in an infectious model.