Proteolytically Inactive Per a 10 Allergen of Periplaneta americana Modulates Th2 Response and Enhances IL-10 in Mouse Model
- 154 Downloads
Purified allergens with reduced IgE reactivity are required to improve the safety and efficacy of allergen-specific immunotherapy (IT).
The present study investigates the efficacy of purified cockroach allergen immunotherapy with proteolytically active and inactive Per a 10 in allergic mouse model.
Balb/c mice were sensitized intraperitoneally with cockroach extract (CE) and purified allergen Per a 10 in separate groups. Mice were treated subcutaneously with phosphate-buffered saline (PBS), CE, active and inactive Per a 10 and challenged intranasally. Antigen specific IgE, IgG1 and IgG2a in serum and cytokines IL-4, IL-13, IFN-γ, IL-10, TGF-β in bronchoalveolar lavage (BAL) fluid and spleen culture supernatant (CS) were estimated by enzyme-linked immunosorbent assay. Lung histology was analyzed by hematoxylin and eosin staining.
IT with Per a 10 demonstrated significant reduction in IgE levels in serum, IL-4 levels in BAL fluid, CS, and eosinophilic infiltration in lungs than PBS-treated mice. This was associated with significantly increased IL-10 secretion in BAL fluid and CS. IT with Per a 10 effectively suppressed T-helper type 2 (Th2) response in mice sensitized with Per a 10 than CE group. Further, IT with inactive Per a 10 showed maximum reduction in systemic and airway inflammation and induced maximum IL-10 release in BAL fluid and CS than other antigens.
IT with Per a 10 effectively suppressed Th2 response and lung inflammation in Per a 10- or CE-sensitized mice. The beneficial effects of IT with inactive Per a 10 are more pronounced than active Per a 10.
KeywordsAnimal model allergen immunotherapy P. americana Per a 10 serine protease
Spleen culture supernatant
Aminoethyl benzenesulfonyl fluoride hydrochloride
N-Benzoyl arginine ethyl ester hydrochloride
Whole body cockroach extract
Sodium dodecyl sulfate
Enzyme-linked immunosorbent assay
One of the authors (Deepsikha) received financial assistance from Council of Scientific and Industrial Research, New Delhi, India.
- 10.Garcia-Robaina JC, Sanchez I, de la Torre F, Fernandez-Caldas E, Casanovas M. Successful management of mite-allergic asthma with modified extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae in a double-blind, placebo-controlled study. J Allergy Clin Immunol. 2006;118:1026–32.CrossRefPubMedGoogle Scholar
- 22.Chapman MD, Vailes LD, Hayden ML, Platts-Mills TAE, Arruda LK. Cockroach allergens and their role in asthma. In: Kay AB, editor. Allergy and allergic diseases. Oxford: Blackwell Science; 1996. p. 942–51.Google Scholar
- 24.Kang BC, Johnson J, Morgan C, Chang JL. The role of immunotherapy in cockroach asthma. J Asthma. 1998;25:205–18.Google Scholar
- 30.Van Oosterhout AJ, Van Esch B, Hofman G, Hofstra CL, Van Ark I, Nijkamp FP, et al. Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma. Am J Respir Cell Mol Biol. 1998;19:622–8.PubMedGoogle Scholar
- 34.Finkelman FD, Katona IM, Urban Jr JF, Holmes J, Ohara J, Tung AS, et al. IL-4 is required to generate and sustain in vivo IgE responses. J Immunol. 1998;141:2335–41.Google Scholar
- 35.Ebner C, Siemann U, Bohle B. Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative response to allergen and shift from Th2 to Th1 in T cell clones specific for Phl p I, a major grass pollen allergen. Clin Exp Allergy. 1997;27:1007–15.CrossRefPubMedGoogle Scholar
- 46.Bousquet J, Becker WM, Hejjaoui A, Chanal I, Lebel B, Dhivert H, et al. Differences in clinical and immunologic reactivity of patients allergic to grass pollens and to multiple pollen species. II. Efficacy of a doubleblind, placebo-controlled, specific immunotherapy with standardized extracts. J Allergy Clin Immunol. 1991;88:43–53.CrossRefPubMedGoogle Scholar