title: Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells.
abstract: 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.
authors.affiliation: Department of Rheumatology, Leiden University Hospital, The Netherlands.
authors.forename: B E
authors.initials: BE
authors.lastname: van den Borne
authors.forename: B A
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: H H
authors.initials: HH
authors.lastname: de Rooij
authors.forename: S
authors.initials: S
authors.lastname: le Cessie
authors.forename: C L
authors.initials: CL
authors.lastname: Verweij
mesh_terms: 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
chemical_list: D002738:Chloroquine; D006886:Hydroxychloroquine; D007371:Interferon-gamma; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors