INCREASED NATURAL-KILLER RESISTANCE TO CYCLOSPORINE-A BY CONTINUOUS DOSES OF DEXAMETHASONE IN RATS

There is a controversy on the effects of physiological levels of gluco corticoids on natural killer (NK) cytotoxity. Therefore, the effects o f exogenously administered dexamethasone on NK cytotoxity in 8-week-ol d male, Fischer 344 rats were studied. We suppose that the reason for the controversy is insufficient sensitivity of the ordinal radioactive chromium-release assay for normal healthy subjects or animals. Theref ore, we developed a new index, a resistance to artificial immunosuppre ssor, cyclosporine A (CsA) using rat NK activity as an indicator, and named this index, increased resistance to immunosuppressor (IRIS). Aft er some basic, characterizing studies, authors confirmed the fact that continuous doses of dexamethasone (DEX) attenuated NK suppression of CsA. In protocol 4, 18 rats were randomly divided into three groups: t he first (DEX+CsA) was injected for 5 days with 0.1 mg DEX/kg/day and a single dose of CsA on the final day, intraperitoneally; the second ( SAL + CsA) was treated with an equal volume of saline and CsA; the thi rd (DEX + SAL) was treated with DEX but not CsA. The IRIS in NK activi ty was increased significantly (P<0.01) with 5 days injection of DEX. These results demonstrated that physiological, and continuous dosage o f glucocorticoids stimulated IRIS in NK activity in rats, and this sug gests that appropriate stimuli through the hypothalamic-adrenal axis m ight be acting, at least, as a defence against immune collapses or dys functions.