Anti-inflammatory effect and selectivity profile of AS1940477, a novel and potent p38 mitogen-activated protein kinase inhibitor.

Given the key role p38 mitogen-activated protein kinase (MAPK) plays in inflammatory responses through the production of cytokines and inflammatory mediators, its inhibition is considered a promising therapeutic strategy for chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, and chronic obstructive pulmonary disease. Here, we evaluated the anti-inflammatory effect and selectivity profile of the novel p38 MAPK inhibitor AS1940477. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms.

Differential effects of FK506 and methotrexate on inflammatory cytokine levels in rat adjuvant-induced arthritis.

Objective: To investigate the effects of prophylactic and therapeutic treatments with FK506 (tacrolimus), an immunosuppressive drug that specifically inhibits T cell activation, and methotrexate (MTX) on inflammatory cytokines, tumor necrosis factor (TNF)-a, interleukin (IL)-1beta, and IL-6 levels in rat adjuvant-induced arthritis (AIA).

Methods: AIA was induced in female Lewis rats. Arthritis was assessed by hindpaw swelling.

Calcineurin inhibitors exert rapid reduction of inflammatory pain in rat adjuvant-induced arthritis.

1. FK506 and cyclosporin A (CsA) are immunosuppressive drugs, that specifically inhibit T-cell activation via calcineurin inhibition. This study was undertaken to investigate whether calcineurin inhibitors exert analgesic actions in rat adjuvant-induced arthritis (AIA), an animal model of rheumatoid arthritis (RA).