Abstract
Background
Eosinophilic Gastrointestinal Disorders (EGIDs) are hypersensitivity disorders frequently triggered by food allergy and manifested by mucosal eosinophilic infiltration at any level of the gastro-intestinal tract. This study established a model of gastric eosinophilia in peanut-sensitized piglets to evaluate the efficacy of epicutaneous immunotherapy (EPIT) for its treatment.
Methods
Experiments were carried out in piglets first sensitized by 3 intra-peritoneal injections of peanut protein extract (PPE) with adjuvant, and then given PPE orally for 10 days, a sequence leading to gastric eosinophilia assessed by endoscopy. For 3 months, 8 piglets received active EPIT, using Viaskin® loaded with PPE, applied daily on the ear, while 8 received placebo EPIT (Placebo). Piglets were exposed to a second 10-day period of PPE orally. Lesions were scored by endoscopy on the last day of PPE exposure. After sacrifice, all parts of the digestive tract were analysed by a pathologist unaware of the piglets' status. IgE response was measured and mechanistic parameters were analyzed in the spleen.
Results
After sensitization, a significant increase of total IgE was observed in sensitized compared to naive animals (61.1±13.3 vs 27.8±6 ng/mL, p<0.01). Following oral intake of PPE, sensitized piglets developed moderate gastritis compared to naive piglets (1.5 vs 1.0, median score). After 3 months of immunotherapy, median IgE was significantly reduced in EPIT vs placebo piglets (61.4±16.3 vs 105.9±25.6 ng/mL, p<0.01). Active EPIT significantly reduced gastric mucosal lesions induced by PPE oral intake (macroscopic score 0 [0-2] vs 2 [1-3], p<0.01, respectively active vs placebo) and gastric mucosa eosinophils counts (239 eosinophils/mm2 [59-645] vs 2554 eosinophils/mm2 [462-8057], p<0.01, respectively active vs placebo). GATA-3, IL-5 and eotaxin mRNA expression decreased significantly after EPIT (p<0.05).
Conclusions
This study describes a large animal model of gastric eosinophil in peanut-sensitized piglets. Utilizing this model, we demonstrated the efficacy of EPIT in treating peanut-induced EGIDs.
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