SUPPRESSION OF INTESTINAL MUCOSAL NATURAL-KILLER-CELLS BY CORTICOSTEROIDS

Background: Corticosteroid therapy of patients with inflammatory bowel disease can give rise to systemic side-effects, Budesonide is a topic ally acting corticosteroid with low systemic bioavailability and is ef ficacious in the treatment of inflammatory bowel disease, Natural kill er cells were previously found to be altered, both systemically and lo cally, in patients with inflammatory bowel disease, Modulatory effects of budesonide, prednisolone, dexamethasone, and cortisol on periphera l blood NK cells have already been described, but have never been asse ssed on mucosal NK cells from the intestine, Methods: The effect of th e synthetic corticosteroids prednisolone and budesonide, the endogenou s corticosteroid cortisol, and adrenocorticotropic hormone was analyse d on NK cells isolated from the lamina propria of human intestinal res ection specimens. Results: The three corticosteroids suppressed intest inal NK cell activity, not only during the cytotoxicity assay, but als o after pre-incubation of the lamina propria mononuclear cells. ACTH, however, did not affect the activity of intestinal NK cells, We previo usly showed that corticosteroid-suppressed peripheral blood NK cell ac tivity could be restored in vivo, but not in vitro, by the administrat ion of ACTH, In the present study, the in vitro incubation of budesoni de- or prednisolone-suppressed mucosal NK cells with cortisol, alone o r combined with ACTH, did not revert the suppressed NK cell activity, These findings are similar to our previous observations with periphera l blood NK cells. Conclusions: Intestinal mucosal NK cells can be supp ressed by systemically as well as locally acting corticosteroids, This suppression in NK cell activity is not reversed by incubation with co rtisol and/or ACTH.