1365-2222/asset/cover.gif?v=1&s=363d6ac7042b7535760df61b7393fd8e0a08e85f "Clinical & Experimental Allergy")
These authors contributed equally to this work.
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Original Articles
Effective treatment of experimental ragweed-induced asthma with STAT-6-IP, a topically delivered cell-penetrating peptide
Article first published online: 20 SEP 2011
DOI: 10.1111/j.1365-2222.2011.03853.x
© 2011 Blackwell Publishing Ltd
Additional Information
How to Cite
- †
These authors contributed equally to this work.
Publication History
- Issue published online: 13 OCT 2011
- Article first published online: 20 SEP 2011
- Manuscript Accepted: 11 JUL 2011
- Manuscript Revised: 7 JUL 2011
- Manuscript Received: 17 MAR 2011
Funded by
- J.T. Costello Memorial Research Fund
- Richard and Edith Strauss Canada Foundation
- le Fonds de la Recherche en Sante du Quebec
- Lloyd Carr-Harris Foundation
- Montreal Children's Hospital Research Institute
- Canadian Institutes of Health Research
Keywords:
- allergic airways;
- animal model;
- asthma;
- immunomodulation;
- ragweed;
- STAT-6;
- treatment
Summary
Background
Treatment of allergic airways disease including asthma remains primarily local immunosuppression with topical corticosteroid and symptomatic management with antihistamines and anti-leucotrienes. We have developed a novel topical therapy designed to specifically inhibit the events associated with Th2 cell activation.
Objective
We assessed the efficacy of our cell-penetrating STAT-6 inhibitory peptide (STAT-6-IP), a novel treatment for allergic airways disease, in a model of chronic ragweed-induced asthma.
Methods
Six- to eight-week-old mice were sensitized over 5 weeks with intranasal (IN) exposures to whole ragweed allergen without adjuvant. Mice were then IN challenged with Amba 1 with and without treatment IN with STAT-6-IP and allergic responses assessed. Two weeks later, some animals were rechallenged with Amba 1 with or without STAT-6-IP.
Results
Animals exposed to IN ragweed developed significant airway hyperresponsiveness and airways inflammation upon challenge. Cell cultures showed increases in Th2 cytokines IL-4 and IL-13. Topical STAT-6-IP treatment reduced production of Th2 cytokines, demonstrated increased expression of IL-10 and reduced frequency of cultured IL-4 positive CD4+ T cells derived from treated mice, suggesting that STAT-6-IP treatment may be immunomodulatory. Airway responsiveness to methacholine challenge in the treatment group was similarly reduced to that of the non-allergic PBS-exposed animals. Importantly, STAT-6-IP-treated mice remained hyporesponsive following second ragweed challenge 2 weeks after treatment.
Conclusions and Clinical Relevance
These data suggest that topical application of the STAT-6-IP is sufficient to inhibit allergic airways responses in animals chronically sensitized and challenged with ragweed. Data show that a single topical treatment course is sufficient to block signs of allergic responses to ragweed in the airways for at least 2 weeks. STAT-6-IP is a novel potential treatment for chronic allergic asthma.