A new insight into effects of a clinically proved combination of methotrexate and hydroxychloroquine
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Combination of methotrexate (MTX) with hydroxychloroquine (HCQ) is one of the most effective therapies used for treatment of rheumatoid arthritis. The aim of the study was to more complexly examine the effect of combination HCQ and MTX on disease progression in arthritic rats focusing on inflammatory markers. Adjuvant arthritis (AA) was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund´s adjuvant in Lewis rats and the disease was monitored 28 days. The experiment included healthy animals, control AA animals, AA animals with administration of HCQ (40 mg/kg b.w. daily, p.o.), AA animals with administration of MTX (0.4 mg/kg b.w. twice a week, p.o.), and AA animals treated with the combination of HCQ + MTX. HCQ in monotherapy reduced only the plasmatic level of IL-1β (day 28). On day 14, MTX + HCQ significantly decreased the plasmatic levels of IL-1β, IL-17 and combination was more effective than MTX in reduction of IL-17. On day 28, combination significantly decreased the plasmatic levels of CRP and IL-1β and it was more effective than MTX in reduction of IL-1β. Expression of IL-1β and inducible NO-synthase total mRNA in lung were most effectively reduced by MTX + HCQ. Combination of MTX + HCQ reduced hind paw volume, arthritic score and increased body mass of animals very effectively (days 14, 21, and 28). In summary, MTX + HCQ were much better than MTX in correcting inflammatory and clinical markers. This study showed in more details that the anti-arthritic effect of MTX + HCQ is particularly due to reduction of the levels of inflammatory cytokines.
KeywordsDrug research Immunoassay Alkaloids Rheumatoid arthritis Cytokines Anti-rheumatic therapy
This work was supported by grants APVV-0052-10, APPV-15-308, and VEGA 2/0045/11.
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