APOPTOSIS OF LYMPHOCYTES INDUCED BY GLUCOCORTICOIDS AND RELATIONSHIP TO THERAPEUTIC EFFICACY IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. Glucocorticoids (GCs) are the drugs of first choice for tre atment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents, This study evaluated the p ossibility of a relationship between response to GC treatment and the rate of apoptosis in vitro, and also analyzed Bcl-2 and Fas expression on peripheral blood mononuclear cells (PBMC) from patients with SLE i n relation to GC-induced apoptosis. Methods. Twenty-seven SLE patients and 13 normal controls were studied. Disease activity scores were det ermined before and after treatment and used to divide patients into 2 groups: GC-resistant and GC-responsive. Isolated PBMC were stimulated with anti-CD3 monoclonal antibodies, cultured with various concentrati ons of GC, and analyzed by alamar blue assay to determine the LC50, de fined as the concentration of GC lethal to 50% of the cells. We measur ed the expression of CD4, CD8, Fas, and Bcl-2 by FACStar plus flow cyt ometry. Results, Lymphocytes in the GC-resistant group of SLE patients showed a significantly lower percentage of GC-induced apoptotic cells than did lymphocytes from the responsive group or from normal control s. The LC,, in the resistant group was significantly higher than that in normal controls or the responsive group. The lymphocytes remaining in the resistant group after GC treatment were mainly CD8+, with a hig h expression of Bcl-2. There was no significant difference in Fas expr ession between the GC-responsive and GC-resistant groups. Conclusion. Determination of the LC50 may be useful in predicting the efficacy of GC treatment in SLE patients, and may be of use in considering other t reatment options. CD8 and Bcl-2 double-positive lymphocytes that are i nsensitive to the apoptotic effect of GCs may play a role in the resis tance to these agents in SLE patients.