Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response

Abstract

Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic activity of GMP was evaluated using a rat ovalbumin (OVA)-induced FA model with gastrointestinal manifestation. Rats were orally GMP treated from 3 days prior and during FA development. The severity of food anaphylaxis and diarrheal episodes, antibody production and histamine level were measured. Histopathological changes, inflammation and predominant cytokine profile at intestine were analyzed. Oral GMP intake decreased clinical signs and diarrhea severity induced by allergen, with a significant reduction in intestinal edema and expression level of IL-1β and TNF-α. Prophylaxis with GMP also diminished serum anti-OVA IgE and IgG1, and histamine levels. GMP treatment markedly decreased eosinophil infiltration, mast cell and goblet cell hyperplasia, total IgE expression in intestine, and prevented histological changes in villi, crypts and internal muscularis layer. The treatment effectively suppressed IL-5, IL-13 and GATA3 expression and skewed the intestinal cytokine profile toward type 1 and regulatory. These results suggest that GMP may protect against FA through down-regulating the type 2 inflammatory response.

Resveratrol Treatment Prevents Increase of Mast Cells in Both Murine OVA Enteritis and IL-10−/− Colitis

“…Elevated presence of MC may be accompanied with enhanced MC activity. The enhancement of proteases levels in food allergy was previously shown [48,57,66]. However, we did not find significant inhibitory effects of resveratrol on mRNA expression of MC proteases in duodenum and colon sections, which have been strongly enhanced in OVAchallenged animals.…”

“…Besides infiltration with inflammatory cells into affected tissues, food allergies are further associated with several histological changes in the intestine [48,[55][56][57]. We observed that tissue damage, evaluated as epithelial barrier disruption, was slightly enhanced in intestinal tissues of OVA mice, with no significant attenuation by resveratrol.…”

“…Food allergy and enteritis are accompanied by histological changes and injury in the gut [50,[54][55][56][57]. We found that OVA-induced allergic enteritis resembles a mild form of inflammation.…”

“…This is in concordance with observations from Brandt et al [28], who showed increased MC numbers in OVA-treated mice and that diarrhea was mediated by MC presence. Increased numbers of MC in affected tissue sections are reported by several studies examining food allergy [59,60] together with elevated levels of MC associated parameters such as MC protease 1 (MCPT1) [24,48,60] or histamine [24,57,61] in the respective intestinal areas or sera. We found that resveratrol treatment for 28 days inhibited the increased MC presence in both GIT sections duodenum and colon.…”

Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects

“…New pharmacological therapies in the management of food allergies aim at regulating inducing cells and suppressing the native and adaptive responses responsible for triggering allergic reactions [65][66][67]. These therapies are not allergen-dependent, acting nonspecifically, which differentiates them from immunotherapy.…”