IL-5 and TNF-alpha participate in recruitment of eosinophils to intestinalmucosa in ulcerative colitis

There is an increased influx of activated eosinophils to the intestinal muc osa in active ulcerative colitis, and an increased release of eosinophil-de rived proteins, such as ECP, has also been observed. These findings indicat e that eosinophils may contribute to tissue damage and intestinal inflammat ion in this disease. The relative importance of different chemotactic facto rs and the impact of steroid treatment on their effect in active ulcerative colitis are not known. We measured the eosinophil chemotactic activity in perfusion fluids from 11 patients with ulcerative colitis before and after steroid treatment and from 7 control patients. The effect of neutralizing a ntibodies to IL-5 and -8, RANTES, eotaxin, MCP-3, TNF-alpha, GM-CSF was inv estigated. The chemotactic activity was higher in perfusion fluids from pat ients than from controls (P = 0.0043). Anti-IL-5 (P = 0.005) and -TNF-alpha (P = 0.017) inhibited the activity in perfusion fluids obtained before tre atment. Steroid treatment prevented the effect of all antibodies but had no significant effect on the chemotactic activity. The chemotactic activity c orrelated with the levels of eosinophil granule proteins in the perfusion f luids. In conclusion, in ulcerative colitis, eosinophils are attracted to t he intestinal tissue by chemotactic factors, of which IL-5 and TNF-alpha ma y be the most prominent steroid-sensitive ones. The steroid-insensitive che motactic activities remain unidentified.