Suppression of lymphocyte interleukin-2 receptor expression by glucocorticoids, cyclosporine, or both.
Although glucocorticoids and cyclosporine are frequently used to treat patients with various types of glomerulopathy, clinical responses to treatment vary considerably. Considerable interindividual heterogeneity in the suppressive effects of glucocorticoids on lymphocyte proliferation in vitro has been previously reported, suggesting that differences in the pharmacodynamic responsiveness of the immune system to these agents might be an important determinant of how well an individual patient responds to treatment. It also has been shown that methylprednisolone is significantly more suppressive than prednisolone. To identify cellular mechanisms by which these drugs act, a study of the suppressive effects of prednisolone, methylprednisolone, and cyclosporine on lymphocyte proliferation and the expression of the cell surface receptor for interleukin-2 (IL-2R) was conducted using phytohemagglutin-stimulated peripheral blood mononuclear cells (PBMCs) from 13 patients with glomerulopathy and 12 control subjects. Heterogeneity among individuals in both parameters of lymphocyte responsiveness to these drugs was again found, and the significantly greater suppressive effect of methylprednisolone was confirmed for both proliferation and IL-2R expression in patients and control subjects. Cyclosporine alone was moderately suppressive. For most individuals, the greatest degree of suppression occurred when cells were exposed to both cyclosporine and glucocorticoid. Further studies are being conducted to determine whether pretreatment assessment of in vitro lymphocyte responsiveness has any predictive value regarding therapeutic efficacy of each drug in individual patients and to identify of those patients likely to require a more intensive or multidrug immunosuppressive regimen.
Briggs
W A
WA
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Gao
Z H
ZH
Xing
J J
JJ
Gimenez
L F
LF
Samaniego
M D
MD
Scheel
P J
PJ
Choi
M J
MJ
Burdick
J F
JF
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000187:drug effects*
D005938:Glucocorticoids; D015375:Receptors, Interleukin-2; D016572:Cyclosporine