Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells.
OBJECTIVE
The efficacy of both chloroquine and hydroxychloroquine in rheumatoid arthritis (RA) has been proved in controlled clinical trials. Despite similar chemical characteristics, it is believed the clinical efficacy of chloroquine is superior to that of hydroxychloroquine in patients with RA. Excessive production of proinflammatory cytokines was shown to contribute to the pathogenesis of RA. From different studies testing either chloroquine or hydroxychloroquine, it could be concluded that both drugs differentially inhibit cytokine production.


METHODS
We compared the effects of both chloroquine and hydroxychloroquine on stimulated peripheral blood mononuclear cells (PBMC) with respect to cytokine production. Therefore, PBMC were tested for tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interferon-gamma (IFN-gamma) by specific ELISA, after stimulation with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) in the presence or absence of different concentrations of chloroquine or hydroxychloroquine.


RESULTS
We observed that chloroquine and hydroxychloroquine equally inhibit PHA induced TNF-alpha and IFN-gamma production, and LPS induced TNF-alpha and IL-6 production, while PHA induced IL-6 production was not affected.


CONCLUSIONS
Chloroquine and hydroxychloroquine display similar effects on PHA and LPS induced cytokine production by PBMC under identical in vitro conditions. These findings may help in understanding the mechanism of action of these drugs on RA.
van den Borne
B E
BE
Department of Rheumatology, Leiden University Hospital, The Netherlands.
Dijkmans
B A
BA
de Rooij
H H
HH
le Cessie
S
S
Verweij
C L
CL
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000093242:Interleukin-6 Inhibitors
D002738:Chloroquine; D006886:Hydroxychloroquine; D007371:Interferon-gamma; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors