Intestinal Alkaline Phosphatase Has Beneficial Effects in Mouse Models of Chronic Colitis

Background: The brush border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and is protective against dextran sulfate sodium (DSS)-induced acute injury in rats. The present study evaluated the potential therapeutic role for orally administered calf IAP (cIAP) in two independent mouse models of chronic colitis: 1) DSS-induced chronic colitis, and 2) chronic spontaneous colitis in Wiskott Aldrich Syndrome protein (WASP)-deficient (knockout) mice that is accelerated by irradiation. Methods: The wildtype (WT) and TAP knockout (IAP-KO) mice received four cycles of 2% DSS ad libitum for 7 days. Each cycle was followed by a 7-day DSS-free interval during which mice received either cIAP or vehicle in the drinking water. The WASP-KO mice received either vehicle or cIAP for 6 weeks beginning on the day of irradiation. Results: Microscopic colitis scores of DSS-treated IAP-KO mice were higher than DSS-treated WT mice (52 +/- 3.8 versus 28.8 +/- 6.6, respectively, P < 0.0001). cIAP treatment attenuated the disease in both groups (KO = 30.7 +/- 6.01, WT = 18.7 +/- 5.0, P < 0.05). In irradiated WASP-KO mice cIAP also attenuated colitis compared to control groups (3.3 +/- 0.52 versus 6.2 +/- 0.34, respectively, P < 0.001). Tissue myeloperoxidase activity and proinflammatory cytokines were significantly decreased by cIAP treatment. Conclusions: Endogenous IAP appears to play a role in protecting the host against chronic colitis. Orally administered cIAP exerts a protective effect in two independent mouse models of chronic colitis and may represent a novel therapy for human IBD.