title: Methotrexate regulates Th-1 response by suppressing caspase-1 and cytokines in psoriasis patients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Physiology and Biochemistry of Exercise, PPGCS, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, Santa Catarina, Brazil.
authors.forename: Anand
authors.initials: A
authors.lastname: Thirupathi
authors.affiliation: Department of Medical Research, SRM Medical College, Hospital and Research Centre, Kattankulathur 603203, Tamilnadu, India. Electronic address: tami24684@gmail.com.
authors.forename: Tamilselvi
authors.initials: T
authors.lastname: Elango
authors.affiliation: Department of Biochemistry, SRM Medical College, Hospital and Research Centre, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Swapna
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Department of Dermatology, SRM Medical College, Hospital and Research Centre, Kattankulathur 603203, Tamilnadu, India.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gnanaraj
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1; D008727:Methotrexate
keywords: Caspase-1; Interleukin-18; Methotrexate; Psoriasis; Th-1 immune cells