Methotrexate regulates Th-1 response by suppressing caspase-1 and cytokines in psoriasis patients

• We observed increased plasma IL-18 and serum TNF-α levels in psoriatic patients.
• MTX treatment led to significant decline in plasma IL-18 and serum TNF-α in psoriatic patients.
• Caspase-1 expression reduced significantly after MTX treatment.

BackgroundCaspase-1 induces the proinflammatory cytokines which appears to be a promising target in Th1-type inflammatory diseases, like psoriasis. We determined the effect of MTX on caspase-1, TNF-α and IL-18 in psoriasis patients.MethodsWe recruited 45 control subjects and 58 psoriasis patients for this study. The patients were treated with 7.5 mg of MTX per week for 12 weeks. Folic acid was given at 5 mg once daily except on the day of MTX for 12 weeks. Blood samples and lesional skin biopsy were taken. Histological examination has been done. IL-18 and TNF-α levels were analyzed by using ELISA. Caspase-1 expression was analyzed by western blot and Real Time PCR.ResultsHistological examinations showed MTX decreased acanthosis in psoriasis skin. Plasma IL-18 level and serum TNF-α were increased in psoriasis and deduced significantly (P < 0.001) after MTX treatment. Protein and mRNA expression of caspase-1 in skin biopsy were higher in psoriasis and reduced significantly (P < 0.001) after MTX treatment.ConclusionDecreasing inflammatory caspase and proinflammatory cytokines by MTX, inhibits the Th1 response in psoriasis. This shows the therapeutic effect of MTX in controlling the immunopathogenesis of psoriasis.