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The hygiene hypothesis proposes that lack of microbial T helper (Th) 1\u2013like stimulation during early childhood leads to increased Th2-driven allergic disorders later in life. Immunostimulatory cytosine-phosphate-guanosine (CpG)\u2013oligodeoxynucleotide motifs are candidate molecules for immunotherapeutic studies, as they have been shown to shift the Th2 response toward the Th1 direction and reduce allergic symptoms. Using natural rubber latex (NRL)\u2013induced murine model of asthma, we demonstrated that intradermal CpG administration with allergen reduced pulmonary eosinophilia, mucus production, and Th2-type cytokines, but unexpectedly induced airway hyperreactivity (AHR) to inhaled methacholine, one of the hallmarks of asthma. We found that induction in AHR was dependent on STAT4, but independent of STAT6 signaling. CpG treatment increased production of IFN-\u03b3 in the airways and shifted the ratio of CD4+:CD8+ T cells toward CD8+ dominance. By blocking soluble IFN-\u03b3 with neutralizing antibody, AHR diminished and the CD4+:CD8+ ratio returned to CD4+ dominance. These results indicate that increased production of IFN-\u03b3 in the lungs may lead to severe side effects, such as enhancement of bronchial hyperreactivity to inhaled allergen. This finding should be taken into consideration when planning prophylaxis treatment of asthma with intradermal CpG injections.<\/jats:p>","DOI":"10.1165\/rcmb.2009-0355oc","type":"journal-article","created":{"date-parts":[[2010,6,25]],"date-time":"2010-06-25T20:49:57Z","timestamp":1277498997000},"page":"639-647","source":"Crossref","is-referenced-by-count":11,"title":["Intradermal Cytosine-Phosphate-Guanosine Treatment Reduces Lung Inflammation but Induces IFN-\u03b3\u2013Mediated Airway Hyperreactivity in a Murine Model of Natural Rubber Latex Allergy"],"prefix":"10.1093","volume":"44","author":[{"given":"Rita","family":"Haapakoski","sequence":"first","affiliation":[{"name":"Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piia","family":"Karisola","sequence":"additional","affiliation":[{"name":"Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational 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