Cutting edge: IL-18-transgenic mice: In vivo evidence of a broad role for IL-18 in modulating immune function

IL-18 has been shown to be a strong cofactor for Th1 T cell development. Ho wever, we previously demonstrated that when IL-18 was combined with IL-2, t here was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells. More recently, we and other groups have reported that IL-18 can pot entially induce IgE, IgG1, and Th2 cytokine production in murine experiment al models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA was expressed. CD8(+)CD44(high) T cells an d macrophages were increased, but B cells were decreased in these mice whil e serum IgE, IgG1, IL-4, and IFN-gamma levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-gamma, IL-4 , IL-5, and IL-13 than control wildtype mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytok ines.