Induction of apoptosis in peripheral blood lymphocytes following treatment in vitro with hydroxychloroquine.
OBJECTIVE
Defective regulation of apoptosis may be central to the development of autoimmune disorders. This study investigated the possibility that the antirheumatic effect of hydroxycholoroquine (HCQ) may be achieved by up-regulation of apoptosis.


METHODS
Peripheral blood lymphocytes collected from normal controls and patients with systemic lupus erythematosus (SLE) were cultured in the presence or absence of a range of concentrations of HCQ. Cells undergoing apoptosis were identified by several standard methods, including morphologic changes, DNA fragmentation, and flow cytometry. For some experiments, lymphocytes were simultaneously stained with antibodies to T cell surface markers and with propidium iodide for dual-stain flow 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 cell subpopulations studied. There was no significant difference between the controls and patients with SLE in terms of the percentage of apoptotic cells detected following treatment with HCQ.


CONCLUSIONS
The present study demonstrated that HCQ induces apoptosis in peripheral blood lymphocytes, which leads to the speculation that HCQ may exert its antirheumatic effect through this mechanism.
Meng
X W
XW
Sydney Children's Hospital, and The University of New South Wales, Australia.
Feller
J M
JM
Ziegler
J B
JB
Pittman
S M
SM
Ireland
C M
CM
D018501:Antirheumatic Agents; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008214:Lymphocytes / Q000166:cytology*; D016176:T-Lymphocyte Subsets / Q000166:cytology
D018501:Antirheumatic Agents; D006886:Hydroxychloroquine