Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils

We have generated mice with a cell type-specific disruption of the Stat3 ge ne in macrophages and neutrophils, The mutant mice are highly susceptible t o endotoxin shock with increased production of inflammatory cytokines such as TNF alpha, IL-1, IFN gamma, and IL-6. Endotoxin-induced production of in flammatory cytokines is augmented because the suppressive effects of IL-10 on inflammatory cytokine production from macrophages and neutrophils are co mpletely abolished. The mice show a polarized immune response toward the Th 1 type and develop chronic enterocolitis with age. Taken together, Stat3 pl ays a critical role in deactivation of macrophages and neutrophils mainly e xerted by IL-10.