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 for treatment of systemic lupus erythematosus (SLE) are potent apoptosis inducers. We examined dexamethasone (DEX)-induced apoptosis and Fas expression in peripheral blood lymphocytes of SLE patients and normal subjects. Peripheral blood lymphocytes were obtained from 40 SLE patients and 18 sex- and age-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 patients than normal controls [median (interquartile range) of mean fluorescence intensity without DEX: 74.9 (50.7-98.0) vs 20.0 (17.7-25.0), p < 0.001; with DEX: 77.9 (56.0-130.5) vs 20.5 (18.6-24.7), p<0.001]. DEX (0.1-5 microM) could also induce apoptosis of lymphocytes from SLE and control subjects in a dose-dependent manner. Elevation of apoptotic susceptibility was more prominent 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 upon DEX treatment in vitro may be related, at least partly, to the pharmacological action of corticosteroids.
Ho
C Y
CY
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT.
Wong
C K
CK
Li
E K
EK
Lam
W K
WK
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019014:fas Receptor / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D019014:fas Receptor; D003907:Dexamethasone