Validation of bovine glycomacropeptide as an intestinal anti-inflammatory nutraceutical in the lymphocyte-transfer model of colitis Ortega-González, Mercedes Capitán-Cañadas, Fermín Requena Méndez, María del Pilar Ocón, Borja Romero-Calvo, Isabel Aranda, Carlos Suárez Ortega, María Dolores Zarzuelo Zurita, Antonio Sánchez De Medina López-Huertas, Fermín Martínez Augustín, María Olga Glycomacropeptide Casein macropeptide Lymphocyte-transfer colitis The authors are grateful to Dr Mercedes González for her assistance and also to Dr Arlette Darfeuille Michaud for providing the bacterial strains. They are also thankful to Davisco Foods International, Inc. for providing GMP. The present study was supported by grants from Fundación Ramón Areces and by the Instituto de Salud Carlos III (PI051625 and PI051651) and the Ministry of Economy and Competitivity (SAF2008-01432, AGL2008-04332, SAF2011-22922 and SAF2011-22812) and by funds from Junta de Andalucía (CTS6736 and CTS164). None of the funders had any role in the design and analysis of the study or in the writing of this article. CIBERehd is funded by the Instituto de Salud Carlos III. M. O.-G., P. R., B. O. and C. A. are funded by the Ministry of Education. The authors' contributions are as follows: M. O.-G., F. C.-C., P. R., B. O., I. R.-C. and C. A. carried out the experiments; M. D. S., A. Z., F. S. d. M. and O. M.-A. designed the experiments; F. S. d. M. and O. M.-A. wrote the manuscript. All authors contributed to the discussion and overall structure of the manuscript. None of the authors has any conflicts of interest to declare. Milk κ-casein-derived bovine glycomacropeptide (GMP) exerts immunomodulatory effects. It exhibits intestinal anti-inflammatory activity in chemically induced models of colitis. However, to validate its clinical usefulness as a nutraceutical, it is important to assess its effects in a model with a closer pathophysiological connection with human inflammatory bowel disease. Therefore, in the present study, we used the lymphocyte-transfer model of colitis in mice and compared the effects of GMP in this model with those obtained in the dextran sulphate sodium (DSS) model. GMP (15 mg/d) resulted in higher body-weight gain and a reduction of the colonic damage score and myeloperoxidase (MPO) activity in Rag1(-/-) mice with colitis induced by the transfer of naïve T cells. The colonic and ileal weight:length ratio was decreased by approximately 25%, albeit non-significantly. GMP treatment reduced the percentage of CD4⁺ interferon (IFN)-γ⁺ cells in mesenteric lymph nodes (MLN). The basal production of IL-6 by MLN obtained from the GMP-treated mice ex vivo was augmented. However, concanavalin A-evoked production was similar. The colonic expression of regenerating islet-derived protein 3γ, S100A8, chemokine (C-X-C motif) ligand 1 and IL-1β was unaffected by GMP, while that of TNF-α and especially IFN-γ was paradoxically increased. In the DSS model, GMP also reduced the activity of colonic MPO, but it failed to alter weight gain or intestinal weight:length ratio. GMP augmented the production of IL-10 by MLN cells and was neutral towards other cytokines, except exhibiting a trend towards increasing the production of IL-6. The lower effect was attributed to the lack of the effect of GMP on epithelial cells. In conclusion, GMP exerts intestinal anti-inflammatory effects in lymphocyte-driven colitis. 2025-12-16T11:52:35Z 2025-12-16T11:52:35Z 2013-11-14 journal article Ortega-González M, Capitán-Cañadas F, Requena P, Ocón B, Romero-Calvo I, Aranda C, Suárez MD, Zarzuelo A, Sánchez de Medina F, Martínez-Augustin O. Validation of bovine glycomacropeptide as an intestinal anti-inflammatory nutraceutical in the lymphocyte-transfer model of colitis. Br J Nutr. 2014 Apr 14;111(7):1202-12. doi: 10.1017/S0007114513003590 0007-1145 1475-2662 https://hdl.handle.net/10481/108858 10.1017/S0007114513003590 eng open access Cambridge University Press