Anti-IL-21 monoclonal antibody reduces disease severity and inflammatory cytokines in a murine model of psoriasis and colitis (97.16)

Abstract IL-21 plays a role in many autoimmune and inflammatory diseases, including psoriasis and inflammatory bowel disease (IBD). To investigate IL-21 antagonism in disease, we evaluated a neutralizing anti-mouse IL-21 mAb in a CD4+CD25- T cell transfer SCID mouse model of psoriasis and colitis. Mice treated prophylactically with IL-21 mAb had significant reductions in colitis and psoriatic-like skin symptoms compared to mice treated with PBS or isotype control mAb. IL-21 mAb-treated mice had 5-7-fold lower average lesional skin scores, 6-7-fold lower average clinical colitis scores and significant reductions in histological indices of colitis compared to controls. Mice treated with IL-21 mAb also had significantly lower serum IL-6, RANTES, TNF-α, and MIP-1β levels compared to controls, further supporting an anti-inflammatory role for IL-21 mAb. In a delayed dosing study, mice treated with IL-21 mAb starting 12 days after T cell transfer had significant reductions in colitis, with 3.5-4-fold lower average colitis scores than control-treated mice. Dose-related reductions in lesional skin scores were also observed. Efficacy of IL-21 mAb was equivalent to or better than an anti-mouse IL-12/23p40 active control mAb. These results demonstrate that IL-21 mAb reduces psoriasis-like disease and colitis in a murine model and suggest that an anti-human IL-21 mAb may have clinical utility in treatment of psoriasis and IBD.