INDUCTION OF APOPTOSIS IN PERIPHERAL-BLOOD LYMPHOCYTES FOLLOWING TREATMENT IN-VITRO WITH HYDROXYCHLOROQUINE

Objective. Defective regulation of apoptosis may be central to the dev elopment of autoimmune disorders. This study investigated the possibil ity that the antirheumatic effect of hydroxycholoroquine (HCQ) mag be achieved by up-regulation of apoptosis. Methods. Peripheral blood lymp hocytes collected from normal controls and patients with systemic lupu s erythematosus (SLE) were cultured in the presence or absence of a ra nge of concentrations of HCQ. Cells undergoing apoptosis were identifi ed by several standard methods, including morphologic changes, DNA fra gmentation, and flow cytometry. For some experiments, lymphocytes were simultaneously stained with antibodies to T cell surface markers and with propidium iodide for dual-stain Bow cytometric studies. Results. HCQ was able to induce apoptosis in peripheral blood lymphocytes in a dose- and time-dependent manner, HCQ induced these changes in all T ce ll subpopulations studied, There was no significant difference between the controls and patients with SLE in terms of the percentage of apop totic cells detected following treatment with HCQ. Conclusion. The pre sent study demonstrated that HCQ induces apoptosis in peripheral blood lymphocytes, which leads to the speculation that HCQ may exert its an tirheumatic effect through this mechanism.