Bovine Glycomacropeptide Has Intestinal Antiinflammatory Effects in Rats with Dextran Sulfate-Induced Colitis

Milk K-casein-derived bovine glycomacropeptide (GMP) has immunomodulatory and bacterial toxin-binding effects, and it has been shown to exert intestinal antiinflammatory activity in the trinitrobenzenesulfonic acid-induced model of colitis. However, its mechanism of action is not well characterized, and it is not known whether GMP is effective in other experimental models. The intestinal antiinflammatory activity of GM P was assessed in the dextran sulfate sodium (DSS)-induced model of rat colitis. DSS as applied at a starting concentration of 5% (wt:v) in drinking water and adjusted when the disease activity index (DAI) increased substantially for 10 d. There were 3 experimental groups: control (no inflammation), DSS, and GMP (GMP-treated rats with DSS-induced colitis). GMP pretreatment 1500 mg . kg(-1) . d(-1), starting 2 d before DSS treatment) reduced the DAI by 60% and lowered the colonic damage score by 44% (P < 0.05). GMP fully normalized the colonic expression of interleukin (IL) 1 beta, IL17, IL23, IL6, transforming growth factor beta, IL10, and Foxp3 as assessed by quantitative RT-PCR. The production of interferon-gamma by mesenteric lymph node cells ex vivo was also normalized by GMP treatment. In contrast, GM P did not change colonic thickening, myeloperoxidase, cyclooxygenase 2, or alkaline phosphatase. Histology analysis showed better preservation of the epithelium and attenuated infiltration and submucosal thickening in rats treated with GM P. We conclude that GMP exerts intestinal antiinflammatory activity in this model, which may be primarily related to actions on Th1 and Th17 lymphocytes and perhaps macrophages. J. Nutr. 140: 2014-2019, 2010.