RESUMO
BACKGROUND AND PURPOSE: Calprotectin is a heterodimer composed of two myeloid-related proteins, S100A8 and S100A9, that is abundant in neutrophils and monocytes/macrophages. Faecal levels of calprotectin are used routinely to monitor inflammatory bowel disease activity. EXPERIMENTAL APPROACH: We aimed to assess the role of calprotectin in intestinal inflammation, using the dextran sulfate sodium model of colitis in mice. Calprotectin was administered (50 or 100 µg·day-1 ) by the intrarectal or by i.p. injection (50 µg·day-1 only). The condition of the mice was characterized by morphological and biochemical methods. KEY RESULTS: Intrarectal calprotectin protected significantly against colitis, as shown by lower levels of macroscopic and microscopic damage, colonic myeloperoxidase activity and decreased expression of TNFα and toll-like receptor 4. IL-17 production by spleen and mesenteric lymph node cells was reduced. Calprotectin had no effect on body weight loss or colonic thickening. There were no effects of calprotectin after i.p. injection. Calprotectin had virtually no effects in control, non-colitic mice. Calprotectin had almost no effect on the colonic microbiota but enhanced barrier function. Treatment of rat IEC18 intestinal epithelial cells in vitro with calprotectin induced output of the chemokines CXL1 and CCL2, involving the receptor for advanced glycation end products- and NFκB. CONCLUSION AND IMPLICATIONS: Calprotectin exerted protective effects in experimental colitis when given by the intrarectal route, by actions that appear to involve effects on the epithelium.
Assuntos
Colite/prevenção & controle , Inflamação/prevenção & controle , Complexo Antígeno L1 Leucocitário/farmacologia , Administração Retal , Animais , Células Cultivadas , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Sulfato de Dextrana/antagonistas & inibidores , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Complexo Antígeno L1 Leucocitário/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The definition of remission in Crohn's disease and ulcerative colitis has evolved to include mucosal healing as a measure of treatment efficacy. Randomized, controlled trials have demonstrated mucosal healing is attainable with the current arsenal of therapies available to treat inflammatory bowel disease. Mucosal healing has been shown to reduce the likelihood of clinical relapse, reduce the risk of future surgeries, and reduce hospitalizations. This review focuses on the latest studies addressing clinical outcomes of mucosal healing in the clinical trial and practice setting.