Lymphocyte responsiveness to glucocorticoids, cyclosporine, or both.
The reason why some patients with glomerular diseases respond to steroid treatment and others do not remains obscure, and it is not possible to prospectively evaluate the probability of response in individual patients. One factor that might contribute to the clinical response to treatment could be the relative sensitivity of a patient's immune system to the suppressive effects of steroids or other immunosuppressive agents. To evaluate this possibility, phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 16 patients with various biopsy-proven glomerulopathies were cultured with prednisolone or methylprednisolone in final concentrations of 10(-5) to 10(-8) mol/L. From the dose-response curves, the concentration of steroid required to cause 50% inhibition (IC50) of the PHA-induced proliferative response was determined. The PBMC from 10 patients also were cultured with 400 ng/mL cyclosporine both alone and with 10(-7) mol/L steroid, and the inhibitory effects were calculated. There was considerable heterogeneity in the sensitivities of individual patients to steroid inhibition, and the mean +/- SEM IC50 was significantly lower for methylprednisolone than for prednisolone. Cyclosporine caused 50% or greater inhibition in 6 of the 10 patients but had < 10% inhibitory effect in 2 patients. In most patients studied, cyclosporine plus steroid was significantly more inhibitory than cyclosporine alone, but the combination was usually no more effective than 10(-7) mol/L methylprednisolone alone. These results are consistent with the hypothesis that differences in the sensitivity of individual patient's immune systems to the immunosuppressive effects of steroids and cyclosporine might contribute to differences in their clinical responsiveness to treatment.
Briggs
W A
WA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Gao
Z H
ZH
Gimenez
L F
LF
Scheel
P J
PJ
Choi
M J
MJ
Burdick
J F
JF
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005921:Glomerulonephritis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D011239:Prednisolone / Q000494:pharmacology
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D008775:Methylprednisolone