Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus.
The serological hallmark of systemic lupus erythematosus (SLE) is the presence of antibodies against double-stranded DNA. However, several studies have suggested that it is not DNA itself, but nucleosomes that are the immunogenic particles involved both in the induction of anti-DNA antibodies, and in the pathophysiology of SLE. Meanwhile, It has been demonstrated that there is an accelerated in vitro apoptosis of lymphocytes from patients with SLE. Therefore, one can postulate that the process of apoptosis may provide a source of nuclear antigens to drive the autoantibody response seen in SLE. Our study has demonstrated that hydroxychloroquine exhibits an anti-apoptotic action and this anti-apoptotic effect is dependent on monocyte coexistence. We used both morphology assessment and fluorescent antibody cell sorter (FACS) analysis to measure the apoptotic percentage of lymphocytes from 25 SLE patients in medium alone (control) or with the addition of different concentrations of hydroxychloroquine. Our results have shown that there is a significant decrease in the percentage of apoptosis at the therapeutic concentration (10(-6) M) as compared with the control (p < 0.05). It has been reported that the anti-rheumatic properties of hydroxychloroquine result from its interference with antigen processing in macrophages and other antigen-presenting cells. We propose that this results in decreased stimulation of autoreactive lymphocytes reactive with self-peptides, and consequently diminution of activation-induced cell death (apoptosis) of mature peripheral lymphocytes.
Liu
S T
ST
Department of Internal Medicine, En Chu Kong Hospital, Taipei and Tainan, ROC.
Wang
C R
CR
Yin
G D
GD
Liu
M F
MF
Lee
G L
GL
Chen
M Y
MY
Chuang
C Y
CY
Chen
C Y
CY
D000165:Acridine Orange; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005456:Fluorescent Dyes; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy*; D008214:Lymphocytes / Q000097:blood* / Q000166:cytology / Q000187:drug effects*; D011419:Propidium; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D016387:Women's Health
D005456:Fluorescent Dyes; D011419:Propidium; D006886:Hydroxychloroquine; D000165:Acridine Orange