Milk κ-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 GMP was assessed in the dextran sulfate sodium (DSS)-induced model of rat colitis. DSS was 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 (500 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) 1β, IL17, IL23, IL6, transforming growth factor β, IL10, and Foxp3 as assessed by quantitative RT-PCR. The production of interferon-γ by mesenteric lymph node cells ex vivo was also normalized by GMP treatment. In contrast, GMP 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 GMP. 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.
Supported by grants from the Instituto de Salud Carlos III (PI051625 and PI051651) and the Ministry of Science and Innovation (SAF2008-01432 and AGL2008-04332). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Instituto de Salud Carlos III. R.L-P. and P.R. are funded by the Ministry of Science and Innovation. R.G. is funded by CIBERehd. The group is a member of the Network for Cooperative Research on Membrane Transport Proteins, cofunded by the Ministerio de Educación y Ciencia, Spain and the European Regional Development Fund (grant no. BFU2007-30688-E/BFI).