Published ahead of print on November 22, 2006, doi:10.1164/rccm.200601-054OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200601-054OC
Helminth-derived Products Inhibit the Development of Allergic Responses in Mice1 Center for Infectious Diseases, University of Würzburg, Würzburg, Germany; 2 Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia, Medellín, Colombia; 3 Department of Pulmonary Research, Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach a.d. Riss, Germany; 4 Division of Allergy and Pulmonology, Department of Pediatrics, Martin-Luther-University, Halle-Wittenberg, Halle, Germany; and 5 Molecular Infection Biology, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany Correspondence and requests for reprints should be addressed to Dr. Klaus Erb, Ph.D., Department of Pulmonary Research, Boehringer-Ingelheim Pharma GmbH & Co. KG, H91-02-01, Birkendorferstr. 65, D-88397 Biberach a.d. Riss, Germany. E-mail: klaus.erb{at}bc.boehringer-ingelheim.com Rationale: Epidemiological studies suggest that infections with helminths protect from the development of asthma. Supporting this view is our published finding that infection with Nippostrongylus brasiliensis decreased ovalbumin-induced Th2 responses in the lung of mice. Objectives: To evaluate if N. brasiliensis excretory–secretory products also prevent the development of asthma. Methods: Mice were immunized with ovalbumin/alum intraperitoneally in the absence or presence of helminthic products and then challenged intranasally with ovalbumin. Six days later, we analyzed if the mice developed Th2 responses in the lung.
Main Results: The application of the helminthic products together with ovalbumin/alum during the sensitization period totally inhibited the development of eosinophilia and goblet cell metaplasia in the airways and also strongly reduced the development of airway hyperreactivity. Allergen-specific IgG1 and IgE serum levels were also strongly reduced. These findings correlated with decreased levels of IL-4 and IL-5 in the airways in product-treated animals. The suppressive effects on the development of allergic responses were independent of the presence of Toll-like receptors 2 and 4, IFN- Conclusion: Our results suggest that helminths suppress the development of asthma by secreting substances that modulate allergic responses without affecting the generation of helminth-specific Th2 immunity. The identification of these products may lead to the design of novel therapeutic intervention strategies for the treatment of asthma.
Key Words: allergy • helminth • Nippostrongylus brasiliensis • products • inhibition
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, and most important, IL-10. Interestingly, suppression was still observed when the helminthic products were heated or treated with proteinase K. Paradoxically, we found that strong helminth product–specific Th2 responses were induced in parallel with the inhibition of ovalbumin-specific responses. 
