Effects of dexamethasone on the expression of Fas molecules and apoptosis of lymphocytes in patients with systemic lupus erythematosus

Previous studies have shown that the autoimmune phenomenon could be caused by defective apoptosis of autoreactive lymphocytes. Corticosteroids used fo r treatment of systemic lupus erythematosus (SLE) are potent apoptosis indu cers. We examined dexamethasone (DEX)-induced apoptosis and Fas expression in peripheral blood lymphocytes of SLE patients and normal subjects. Periph eral blood lymphocytes were obtained from 40 SLE patients and 18 sex- and a ge-matched control subjects. Percentages of apoptosis and expression of Fas molecule in lymphocytes were assessed by flow cytometry. Fas expression in lymphocytes treated with or without DEX was significantly higher in SLE pa tients than normal controls [median (interquartile range) of mean fluoresce nce intensity without DEX: 74.9 (50.7-98.0) vs 20.0 (17.7-25.0), p<0.001; w ith DEX: 77.9 (56.0-130.5) vs 20.5 (18.6-24.7). p<0.001], DEX (0.1-5 muM) c ould also induce apoptosis of lymphocytes from SLE and control subjects in a dose-dependent manner. Elevation of apoptotic susceptibility was more pro minent in DEX-treated SLE lymphocytes [33.9% (24.7-37.5%) vs 19.6% (13.6-26 .1%), p = 0.003]. The higher apoptotic susceptibility of SLE lymphocytes up on DEX treatment in vitro may be related, at least partly, to the pharmacol ogical action of corticosteroids.