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Methotrexate regulates Th-1 response by suppressing caspase-1 and cytokines in psoriasis patients
Anand Thirupathi1, Tamilselvi Elango2, Swapna Subramanian3
1Laboratory of Physiology and Biochemistry of Exercise, PPGCS, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, Santa Catarina, Brazil.
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.
Insights
Methotrexate (MTX) treatment significantly reduced caspase-1, tumor necrosis factor-alpha (TNF-α), and interleukin-18 (IL-18) levels in psoriasis patients. This indicates MTX effectively controls the immune response in psoriasis.
Area of Science:
- Dermatology
- Immunology
- Pharmacology
Background:
- Psoriasis is a Th1-type inflammatory disease.
- Caspase-1 and its induced cytokines are potential therapeutic targets.
- The effect of methotrexate (MTX) on these targets in psoriasis was investigated.
Purpose of the Study:
- To determine the effect of MTX on caspase-1, TNF-α, and IL-18 in psoriasis patients.
- To evaluate MTX's role in the immunopathogenesis of psoriasis.
Main Methods:
- 58 psoriasis patients received 7.5mg MTX weekly for 12 weeks.
- IL-18 and TNF-α levels were measured using ELISA.
- Caspase-1 expression was analyzed via Western blot and Real Time PCR.
Main Results:
- MTX treatment reduced skin acanthosis.
- Plasma IL-18 and serum TNF-α levels decreased significantly post-MTX therapy (P<0.001).
- Skin caspase-1 protein and mRNA expression were significantly reduced by MTX (P<0.001).
Conclusions:
- MTX decreases inflammatory caspase and proinflammatory cytokines in psoriasis.
- MTX treatment inhibits the Th1 response, demonstrating therapeutic efficacy.
- MTX plays a role in controlling psoriasis immunopathogenesis.
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