DIFFERENTIAL GLUCOCORTICOID RESPONSIVENESS OF HEMODIALYSIS-PATIENTS LYMPHOCYTES

Acute allograft rejection remains a problem after renal transplantatio n, even in the cyclosporine era. Interindividual differences in the ph armacodynamic responses of the immune system to immunosuppressive agen ts might contribute to the vulnerability of some patients to rejection . Having previously demonstrated decreased sensitivity of hemodialysis patients' lymphocytes to glucocorticoid suppression of mitogen induce d proliferation, the authors undertook a separate study to assess the suppressive effect of glucocorticoids on lymphocyte responsiveness to allogeneic cells and mitogenic stimulation. Lymphocytes were isolated from 32 hemodialysis patients in clinically stable condition for studi es in both phytohemagglutinin (PHA) stimulated cultures and in one-way mixed lymphocyte (MLR) cultures. From the concentration-response rela tionships derived from stimulated cultures with 10(-6), 10(-7) and 10( -8) M concentrations of prednisolone and methylprednisolone, the conce ntration of steroid required to achieve 50% inhibition (IC50) Of lymph ocyte proliferation was determined. A broad range of IC50 values was f ound in both PHA and MLR cultures, but within individual patients, the IC50 values for both steroids correlated significantly between PHA an d MLR cultures. The inhibitory effect of methylprednisolone was signif icantly greater than that of prednisolone in both PHA and MLR cultures . These results demonstrate a heterogeneity of pharmacodynamic respons iveness to prednisolone and methylprednisolone that is consistent with in individuals in two in vitro models of cellular immune response. Pre transplant evaluation by these methods may help identify patients at r isk of suboptimal immunosuppression and assist in selecting the steroi d component of the immunosuppressive regimen.