B-FAHF-2 plus oral immunotherapy (OIT) is safer and more effective than OIT alone in a murine model of concurrent peanut/tree nut allergy

K. D. Srivastava, Y. Song, N. Yang, C. Liu, I. E. Goldberg, A. Nowak-Węgrzyn, H. A. Sampson, X. M. Li

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background: Concurrent sensitization to peanut (PN) and tree nuts (TN), the most dangerous food allergies, is common. Current oral immunotherapy (OIT) is not fully satisfactory. Objective: To determine whether the herbal formula B-FAHF-2 (BF2) ameliorates PN/TN OIT adverse reactions and enhances persistence of a tolerant state. Methods: Concurrently sensitized PN-, walnut- (WN) and cashew (CSH)-allergic mice received 1-day PN/WN/CSH rush OIT plus 3 weeks of maintenance dosing, with or without 3 weeks prior and 3 weeks BF2 co-treatment. Anaphylactic symptom scores, core body temperatures, plasma histamine levels, basophil numbers, antigen-specific IgE, cytokine levels, and IL-4, INF-γ and Foxp3 gene promoter DNA methylation status, and their correlation with final challenge symptom scores were determined. Results: BF2+OIT-treated mice experienced significantly fewer and less severe adverse reactions than OIT-only-treated mice (P<.01) during the 1-day rush OIT build-up dose phase. Both OIT-only and BF2+OIT mice showed significant desensitization (P<.01 and.001, respectively) at 1 week post-therapy challenge, being greater in BF2+OIT mice. All sham-treated and 91% of OIT-treated mice experienced anaphylaxis whereas only 21% of BF2+OIT-treated mice exhibited reactions during 5-6 weeks of dose escalation single PN and TN challenges. Greater and more persistent protection in BF2+OIT mice was associated with significantly lower plasma histamine and IgE levels, increased IFN-γ/IL-4 and IL-10/IL-4 ratios, DNA remethylation at the IL-4 promoter and demethylation at IFN-γ and Foxp3 promoters. Final challenge symptom scores were inversely correlated with IL-4 DNA methylation levels (P<.0002) and positively correlated with IFN-γ and Foxp3 gene promoter methylation levels (P<.0011) (P<.0165). Conclusions and Clinical Relevance: Combined BF2/OIT therapy was safer and produced longer post-treatment protection and more tolerance-prone immunological and epigenetic modifications than OIT alone. BF2/OIT may provide an additional OIT option for patients with concurrent PN/TN and other food allergies.

Original languageEnglish
Pages (from-to)1038-1049
Number of pages12
JournalClinical and Experimental Allergy
Issue number8
StatePublished - Aug 2017


  • B-FAHF-2
  • Chinese herbal medicine
  • Food allergies
  • cytokines and epigenetic regulation
  • murine model of peanut allergies and tree nut allergies
  • oral immunotherapy


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