Increased natural killer resistance to cyclosporine A by continuous doses of dexamethasone in rats

Abstract

SUMMARYThere is a controversy on the effects of physiological levels of glucocorticoids on natural killer (NK ) cytotoxity. Therefore, the effects of exogenously administered dexamethasone on NK cytotoxity in 8-week-old 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. Therefore, we developed a new index, a resistance to artificial immunosuppressor, cyclosporine A (CsA) using rat NK activity as an indicator, and named this index, increased resistance to immunosuppressor (IRIS ). After 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: the 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 third (DEX+SAL) was treated with DEX but not CsA. The IRIS in NK activity was increased significantly (P<0·01) with 5 days injection of DEX. These results demonstrated that physiological, and continuous dosage of glucocorticoids stimulated IRIS in NK activity in rats, and this suggests that appropriate stimuli through the hypothalamic-adrenal axis might be acting, at least, as a defence against immune collapses or dysfunctions.