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

Background: Caspase-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.

Methods: We recruited 45 control subjects and 58 psoriasis patients for this study. The patients were treated with 7.5mg of MTX per week for 12weeks. Folic acid was given at 5mg once daily except on the day of MTX for 12weeks. 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.

Results: Histological 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.

Conclusion: Decreasing 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.