There is considerable evidence that inflammatory bowel disease (IBD), and a variety of other inflammatory disorders, reflect an excessive Th1 response. However, as we shall see below, a number of studies depleting the known members of this inflammatory cascade have reported some “residual” pathology and suggested that “other mediators” may also be involved. A study by Chikano and colleagues1 suggests that interleukin 18 (IL-18) may be one of the villains.

The characteristic cytokine produced by Th1 cells, interferon γ (IFN-γ), has been shown to play a role in the pathogenesis of a number of autoimmune and inflammatory disorders2 and has long been suspected of a role in IBD. Administration of IFN-γ produces small intestinal pathology in mice3 ,4 while elevated IFN-γ expression and increased numbers of IFN-γ secreting cells have been reported in human IBD and are a feature of many of the murine models of IBD.5 ,6 The importance of IFN-γ in such situations has been highlighted by the ability of in vivo depletion of this cytokine to ameliorate disease in a number of models of gastrointestinal pathology. However, more recent studies in a variety of models of IBD have revealed some inconsistencies.5 ,7 Some reports have suggested IFN-γ knockout (KO) CD4⁺ T cells are incapable of inducing colitis and wasting, others have reported comparable disease in IFN-γ^null and wild type (WT) animals, while a recent study7 suggests …