Endogenous IL-12 is required for control of Th2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice.

摘要: We investigated the mechanisms by which treatment with anti-IL-12 Ab prevents cure of infection Leishmania major in resistant C57BL/6 mice. Consistent delayed production IL-12, Abs could be administered as late 2 wk after to exacerbate disease. Starting at infection, cultured lymph node cells from mice treated either polyclonal or monoclonal persistently generated 3- 10-fold more IL-4 and IL-10 response L. Ag compared receiving preimmune goat IgG. Reciprocal decreases Ag-specific IFN-gamma were observed Abs. A similar reversal accompanied progressive disease induced pretreatment a single dose anti-IFN-gamma mAb. Although was suppressed for up 4 anti-IFN-gamma, coadministration neutralizing anti-IL-4 IgG reversed illness. These findings demonstrate that IL-12 produced vivo is necessary both emergence producing down-regulation Th2 cell responses during murine leishmaniasis. Furthermore, uninhibited required sustain initiated decreased synthesis anti-IFN-gamma-treated