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Current oral immunotherapy (OIT<\/jats:styled-content>) is not fully satisfactory.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine whether the herbal formula B\u2010FAHF<\/jats:styled-content>\u20102 (BF<\/jats:styled-content>2) ameliorates PN<\/jats:styled-content>\/TN OIT<\/jats:styled-content> adverse reactions and enhances persistence of a tolerant state.<\/jats:p><\/jats:sec>Methods<\/jats:title>Concurrently sensitized PN\u2010, walnut\u2010 (WN<\/jats:styled-content>) and cashew (CSH<\/jats:styled-content>)\u2010allergic mice received 1\u2010day PN<\/jats:styled-content>\/WN<\/jats:styled-content>\/CSH<\/jats:styled-content> rush OIT<\/jats:styled-content> plus 3\u00a0weeks of maintenance dosing, with or without 3\u00a0weeks prior and 3\u00a0weeks BF<\/jats:styled-content>2 co\u2010treatment. Anaphylactic symptom scores, core body temperatures, plasma histamine levels, basophil numbers, antigen\u2010specific IgE, cytokine levels, and IL<\/jats:styled-content>\u20104, INF<\/jats:styled-content>\u2010\u03b3 and Foxp3 gene promoter DNA<\/jats:styled-content> methylation status, and their correlation with final challenge symptom scores were determined.<\/jats:p><\/jats:sec>Results<\/jats:title>BF<\/jats:styled-content>2+OIT<\/jats:styled-content>\u2010treated mice experienced significantly fewer and less severe adverse reactions than OIT<\/jats:styled-content>\u2010only\u2010treated mice (P<\/jats:italic><.01) during the 1\u2010day rush OIT<\/jats:styled-content> build\u2010up dose phase. Both OIT<\/jats:styled-content>\u2010only and BF<\/jats:styled-content>2+OIT<\/jats:styled-content> mice showed significant desensitization (P<\/jats:italic><.01 and .001, respectively) at 1\u00a0week post\u2010therapy challenge, being greater in BF<\/jats:styled-content>2+OIT<\/jats:styled-content> mice. All sham\u2010treated and 91% of OIT<\/jats:styled-content>\u2010treated mice experienced anaphylaxis whereas only 21% of BF<\/jats:styled-content>2+OIT<\/jats:styled-content>\u2010treated mice exhibited reactions during 5\u20106\u00a0weeks of dose escalation single PN<\/jats:styled-content> and TN<\/jats:styled-content> challenges. Greater and more persistent protection in BF<\/jats:styled-content>2+OIT<\/jats:styled-content> mice was associated with significantly lower plasma histamine and IgE levels, increased IFN<\/jats:styled-content>\u2010\u03b3\/IL<\/jats:styled-content>\u20104 and IL<\/jats:styled-content>\u201010\/IL<\/jats:styled-content>\u20104 ratios, DNA<\/jats:styled-content> remethylation at the IL<\/jats:styled-content>\u20104 promoter and demethylation at IFN<\/jats:styled-content>\u2010\u03b3 and Foxp3 promoters. Final challenge symptom scores were inversely correlated with IL<\/jats:styled-content>\u20104 DNA<\/jats:styled-content> methylation levels (P<\/jats:italic><.0002) and positively correlated with IFN<\/jats:styled-content>\u2010\u03b3 and Foxp3 gene promoter methylation levels (P<\/jats:italic><.0011) (P<\/jats:italic><.0165).<\/jats:p><\/jats:sec>Conclusions and Clinical Relevance<\/jats:title>Combined BF<\/jats:styled-content>2\/OIT<\/jats:styled-content> therapy was safer and produced longer post\u2010treatment protection and more tolerance\u2010prone immunological and epigenetic modifications than OIT<\/jats:styled-content> alone. BF<\/jats:styled-content>2\/OIT<\/jats:styled-content> may provide an additional OIT<\/jats:styled-content> option for patients with concurrent PN\/TN and other food allergies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12936","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T08:42:37Z","timestamp":1491900157000},"page":"1038-1049","source":"Crossref","is-referenced-by-count":31,"title":["B\u2010FAHF<\/scp>\u20102 plus oral immunotherapy (OIT<\/scp>) is safer and more effective than OIT<\/scp> alone in a murine model of concurrent peanut\/tree nut allergy"],"prefix":"10.1111","volume":"47","author":[{"given":"K. 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