title: Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis.
abstract: Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT). Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI) ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% w/w) or milk proteins (Control diet), from day 21 (weaning) until day 56. Leucocytes in mesenteric lymph nodes (MLN) and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05). The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05) and SBI supplementation reduced this variable (p < 0.05). The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05). In the colon of KO mice, there was an increased production of mucosal pro-inflammatory cytokines such as IL-2 (2-fold), IL-6 (26-fold) and IL-17 (19-fold), and of chemokines MIP-1β (4.5-fold) and MCP-1 (7.2-fold). These effects were significantly prevented by SBI (p < 0.05). SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis.
authors.affiliation: Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació and Institut de Nutrició i Seguretat Alimentària, Universitat de Barcelona (UB), Barcelona, Spain.
authors.forename: Anna
authors.identifier: 0000-0003-2175-9684
authors.initials: A
authors.lastname: Pérez-Bosque
authors.affiliation: Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació and Institut de Nutrició i Seguretat Alimentària, Universitat de Barcelona (UB), Barcelona, Spain.
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Miró
authors.affiliation: Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació and Institut de Nutrició i Seguretat Alimentària, Universitat de Barcelona (UB), Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Maijó
authors.affiliation: APC Europe S.A., Granollers, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Polo
authors.affiliation: APC Inc, Ankeny, IA, United States of America.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Campbell
authors.affiliation: APC Inc, Ankeny, IA, United States of America.
authors.forename: Louis
authors.initials: L
authors.lastname: Russell
authors.affiliation: APC Inc, Ankeny, IA, United States of America.
authors.forename: Joe D
authors.initials: JD
authors.lastname: Crenshaw
authors.affiliation: EnteraHealth, Cary, NC, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Weaver
authors.affiliation: Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació and Institut de Nutrició i Seguretat Alimentària, Universitat de Barcelona (UB), Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Moretó
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002417:Cattle; D003092:Colitis / Q000276:immunology*; D003106:Colon / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D007136:Immunoglobulins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology; D044967:Serum / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D007155:Immunologic Factors; D018836:Inflammation Mediators