Suppression of dialysis patients' lumphocyte IL-2R expression by glucocorticoids and cyclosporine

Previous studies have shown interindividual heterogeneity in the suppressive effects of glucocorticoids and cyclosporine (CsA) on the proliferation responses of dialysis patients' peripheral blood mononuclear cells (PBMC). In addition, methylprednisolone (MP) was shown to be significantly more suppressive than prednisolone (P), and PBMC from patients on peritoneal dialysis (PD) were found to be more sensitive to both glucocorticoids than those from patients on haemodialysis (HD). In order to begin to explore the cellular mechanism(s) underlying these observations, the differential suppressive effects of these drugs on lymphocyte interleukin 2 receptor (IL-2R) expression by mitogen-stimulated PBMC from 23 PD and 30 HD were determined. The mean ± SD concentrations (ng/ml) of steroid causing 50% inhibition (IC₅₀) of cell proliferation was significantly lower for PD than HD PBMC with both P (94 ± 93 vs 148 ± 105, P < 0.05) and MP (21 ± 25 vs 35 ± 31, P < 0.05). MP was significantly (P < 0.001) more suppressive than P of IL-2R expression in both PD and HD. PD IL-2R expression was significantly (P < 0.05) more suppressed by CsA alone and by 400 ng/ml CsA + 10^-7 M P than was HD IL-2R expression. CsA + 10^-7 M MP was significantly (P < 0.001) more suppressive of IL-2R expression than the other drugs, alone or in combination, in both groups of patients. In conclusion, these results support the notion that at least one mechanism underlying the significantly greater efficacy of MP compared to P in suppressing PBMC proliferation is its significantly greater suppression of lymphocyte IL-2R expression, either alone or in combination with CsA. Thus, use of MP following allograft transplantation may result in more effective immunosuppression for many recipients.