- 作者：Katherine Arias ; Moiz Baig ; Marc Colangelo ; Derek Chu ; Tina Walker ; Susanna Goncharova ; Anthony Coyle ; Peter Vadas ; Susan Waserman ; Manel Jordana
- 关键词：Peanut allergy ; anaphylaxis ; mast cells ; histamine ; PAF ; leukotrienes ; mathematical modeling
- 刊名：Journal of Allergy and Clinical Immunology
- 出版年：2009
- 出版时间：August 2009
- 年：2009
- 卷：124
- 期：2
- 页码：307-314.e2
- 全文大小：597 K
Background
Food anaphylaxis is an acute and life-threatening systemic allergic reaction. Fatality registries place peanut as the most common culprit of fatal and near-fatal reactions in North America. Because prophylaxis and treatment have advanced little in recent years, it is imperative to evaluate novel therapies.Objective
To investigate the impact of blocking mast cell mediators in a mouse model of peanut-induced anaphylaxis.
Methods
Mice were sensitized with peanut protein and cholera toxin via oral gavage weekly for 4 weeks. One week after the last sensitization, separate groups of mice were treated with either a (1) 5-lypoxygenase inhibitor, (2) a platelet-activating factor (PAF) receptor antagonist, (3) histamine receptor antagonists, or (4) a PAF receptor antagonist along with histamine receptor antagonists before peanut challenge.
Results
Treatment targeting either leukotrienes or histamine alone had no beneficial effects. In contrast, PAF antagonism significantly attenuated the magnitude and duration of the anaphylactic reactions. Particularly, it prevented severe reactions. Moreover, 83 % of PAF-treated versus 43 % of untreated mice reached recovery within 120 minutes after peanut challenge. Notably, combined blockade of PAF and histamine had a clearly greater beneficial effect. In fact, all but 1 mouse developed mild, if any, anaphylactic reactions. In addition, combination therapy was associated with a significant decrease in vascular leakage and release of vasoactive mediators after peanut challenge.
Conclusion
Combination therapy blocking both PAF and histamine markedly reduces the severity of peanut-induced anaphylaxis, and thus it may be a potential life-saving therapeutic approach in peanut and, likely, other food-induced anaphylaxis.