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.
Highlights
Inflammatory bowel diseases (IBD) are characterized by diffuse chronic intestinal inflammation, typically involving neutrophil infiltration, the production of inflammatory mediators, and alterations in the colon barrier that are usually life-long in nature [1]
Scores for the disease activity index (DAI), used to quantify the clinical signs of colitis at the end of the experimental period, were three-fold higher in mdr1-/- mice than in Wild type (WT) mice, and serum-derived bovine immunoglobulin/protein isolate (SBI) administration tended to induce a reduction in DAI scores, as reported elsewhere [15]
Leukocyte recruitment in mesenteric lymph nodes (MLN) and in lamina propria were markedly stimulated in KO mice
Summary
Inflammatory bowel diseases (IBD) are characterized by diffuse chronic intestinal inflammation, typically involving neutrophil infiltration, the production of inflammatory mediators, and alterations in the colon barrier that are usually life-long in nature [1]. The etiopathogenesis of IBD has not been clearly elucidated, but it involves a complex interplay of genetic, environmental, microbial, and immune factors, which alter the barrier properties of the mucous and epithelial layers This allows luminal toxins and antigens to penetrate the mucosa and challenge the gut-associated lymphoid tissue (GALT). The treatment of IBD is mainly pharmacological and involves anti-inflammatory drugs and agents that reduce the symptoms associated with IBD [3] These therapies ameliorate IBD, but their use for long periods of time may result in adverse side effects, including immune suppression [4]. For these reasons, nutrition emerges as an alternative to drug therapies, and food choice has become a promising tool for the treatment and prevention of IBD [5]. Both SDP and IC reduce the activation of Th lymphocytes [12], prevent the release of pro-inflammatory cytokines [13] and restore impaired barrier function [14], in a rat model of intestinal inflammation induced by the S. aureus enterotoxin B
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