Concurrent blockade of platelet-activating factor and histamine prevents life-threatening peanut-induced anaphylactic reactions - 20/08/11
Reprint requests: Manel Jordana, MD, PhD, Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, MDCL Room 4013, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Peanut allergy, anaphylaxis, mast cells, histamine, PAF, leukotrienes, mathematical modeling
Abbreviations used : 5-LO, AU, cysLT, MC, PA, PAF, PAF-R, PIA, PL
Plan
| Supported by Anaphylaxis Canada, the Food Allergy Initiative Organization (New York, NY) and AllerGen Network Centre of Excellence (NCE). M.J. holds a Senior Canada Research Chair on the Immunobiology of Respiratory Diseases and Allergy. K.A. holds an Eva Lillian Cope Research Scholarship. |
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| Disclosure of potential conflict of interest: P. Vadas, S. Waserman, and M. Jordana have received research support from Anaphylaxis Canada and AllerGen NCE. S. Waserman and M. Jordana have also received research support from the Food Allergy Initiative Organization. The rest of the authors have declared that they have no conflict of interest. |
Vol 124 - N° 2
P. 307 - août 2009 Retour au numéro
Article précédent
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