IL-18 induction of IgE: dependence on CD4(+) T cells, IL-4 and STAT6

Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (T(H)2) c ytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in all ergic disorders. Although it is known that IL-4 is critical to the polariza tion of naive CD4(+) T cells to a T(H)2 phenotype, both in vitro and in man y in vivo systems, other factors that regulate in vivo IL-4 production and T(H)2 commitment are poorly understood. IL-18, an IL-1-like cytokine that r equires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4(+) T cells-, IL-4- and STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could induce naive CD4(+) T cells to develop into IL-4-producing cells in vitro. Thus, caspase-1 and IL-18 ma y be critical in regulation of IgE production in vivo, providing a potentia l therapeutic target for allergic disorders.