Functional interactions between mucosal IL-1, IL-ra and TGF-beta 1 in ulcerative colitis

Abstract

Objective: Studies aiming to define key cytokines in inflammatory bowel disease have been restricted to gene expression or protein quantitation but lack functional information on cytokine interactions. Some of the major cytokines that govern the extent and duration of the inflammatory process in ulcerative colitis (UC), appear to be interleukin 1 (IL-1), its natural inhibitor IL-1 receptor antagonist (IL-1ra) and transforming growth factor beta1 (TGF-beta 1). Indeed, as a predictor of inflammation, the mucosal status of IL-1, depicted as a ratio of IL-1ra/IL-1, has often been used.

Methods: Using an IL-1 bioassay and specific anti-cytokine antibodies we have identified the functional role of these cytokines and their interactions in mucosal biopsy samples taken from patients with UC.

Results: Compared with control specimens, the secreted and tissue levels of IL-1 were consistently raised in UC samples. Levels of IL-1, rather than IL-1ra or the ratio of IL-1ra/IL-1, most closely mirrored the severity of inflammation. Using specific antibodies we showed that IL-1ra and TGF-beta 1 appear to modulate the degree of inflammation at different stages of the inflammatory process. Only in severely inflamed tissue, when IL-1 levels were high did IL-1ra inhibit IL-1-induced activity. In contrast, the levels of TGF-beta 1, and its effect in controlling inflammation, was most marked in mild but not severe UC.

Conclusions: The functional roles of these cytokines in the inflammatory process can now be more carefully elucidated using a bioassay and specific neutralising antibodies.