Interleukin (IL)-10/mice spontaneously develop intestinal inflammation characterized by discontinuous transmural lesions affecting the small and large intestine and by dysregulated production of proinflammatory cytokines. The uncontrolled generation of IFN--producing CD4 T cells (Th1 type) has been shown to play a causal role in the development of enterocolitis affecting these mutants. This article discusses studies of IL-10/mice that have investigated the role of enteric organisms in triggering intestinal disease, the mediators responsible for initiating and maintaining intestinal disease, the role IL-10 plays in the generation and/or function of regulatory cells, and the results of IL-10 therapy in experimental animal models of inflammatory bowel disease (IBD) and human patients with IBD. interleukin; counterregulation by IL-10; proinflammatory cytokines; Th1-mediated intestinal disease; IL-10 therapy

BEFORE THE GENERATION OF interleukin (IL)-10/mice, it had already been established that IL-10 was an anti-inflammatory molecule capable of suppressing the in vitro production of numerous cytokines by macrophages, dendritic cells, T cells, and natural killer (NK) cells (21). IL-10 was firmly established as an essential regulator of mucosal responses when it was recognized that enterocolitis was manifested by IL-10/mice and by mice with a disruption in the gene encoding an IL-10 receptor component (CRF2–4/)(16, 30). In addition to IL-10/mice, other rodents with gene-targeted mutations develop intestinal disease due to immune imbalances created by either deleting or overexpressing genes encoding cytokines or other immune components. For example, intestinal inflammation was present in rodents rendered deficient in IL-2, IL-2R, T cell receptor (TCR)-, TCR-, Gi-2, or trans-