EFFECT OF CORTISOL AND ACTH ON CORTICOSTEROID-SUPPRESSED PERIPHERAL-BLOOD NATURAL-KILLER-CELLS FROM HEALTHY-VOLUNTEERS AND PATIENTS WITH CROHNS-DISEASE

Recently, we have shown that administration of adrenocorticotropic hor mone (ACTH) to corticosteroid-treated Crohn's disease (CD) patients in creased the peripheral blood natural killer (NK) cell activity which w as suppressed by the corticosteroids, To elucidate this observation we analysed the in vitro effect of budesonide, prednisolone, cortisol, a nd ACTH on NK cells of healthy volunteers and corticosteroid-treated C D patients. Incubation of peripheral blood mononuclear cells (PBMNC) f rom healthy volunteers during the cytotoxicity assay caused a dose-dep endent inhibition of NK cell activity by the three corticosteroids, wh ile ACTH had hardly any effect. Pre-incubation for 18 h with high and low inhibiting high concentrations also showed a significant inhibitin g effect on NK cell activity of the corticosteroids, The percentage of CD56(+) NK cells tended to increase after pre-incubation with a high inhibiting concentration of budesonide, prednisolone, and cortisol. In cubation of budesonide- or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with ACTH and/or cortisol, to mimic the in vivo situation, did nor restore the corticosteroid-induced suppressio n of NK cell activity. The increase of the budesonide- or prednisolone -suppressed NK cell activity after in vivo administration of ACTH to t he CD patients is therefore probably not a direct effect of cortisol o r ACTH. Presumably other factors like cytokines and/or neurohormones m ust be involved in the in vivo interaction between corticosteroids, AC TH, and NK cells.