Qu, C. et al. Induction of tolerance after establishment of peanut allergy by the food allergy herbal formula-2 is associated with upregulation of interferon-gamma. Clin. Exp. Allergy 37, 846-855

Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Clinical & Experimental Allergy (Impact Factor: 4.77). 07/2007; 37(6):846-55. DOI: 10.1111/j.1365-2222.2007.02718.x
Source: PubMed


Peanut (PN)-anaphylaxis is potentially life threatening. We previously reported that a Chinese herbal medicine preparation, food allergy herbal formula-2 (FAHF-2), prevented peanut allergy (PNA) in mice when administered during sensitization.
To investigate whether FAHF-2 also can prevent anaphylactic reactions when administered to mice with established PNA and, if so, whether protection would persist after cessation of therapy.
C3H/HeJ mice sensitized and boosted over 8 weeks with a standard protocol known to establish PN hypersensitivity received seven weeks of FAHF-2 treatment or water as a sham treatment. Mice were subsequently challenged with PN at week 14 (1-day post-therapy) and week 18 (4-week post-therapy) to evaluate the efficacy and persistence of FAHF-2 treatment by assessing anaphylactic scores, core body temperatures and plasma histamine levels. Serum PN-specific antibody levels and cytokine profiles from splenocytes and mesenteric lymph node (MLN) cells were also determined.
All sham-treated mice challenged at weeks 14 and 18 showed anaphylactic symptoms. In contrast, FAHF-2-treated mice showed no sign of anaphylactic reactions. PN-specific IgE levels in FAHF-2-treated mice also were reduced whereas IgG2a levels were increased. Furthermore, MLN cells from FAHF-2-treated mice produced markedly less IL-4 and IL-5, but more IFN-gamma, and contained increased numbers of IFN-gamma-producing CD8+ cells as compared with sham-treated mice.
FAHF-2 treatment established PN tolerance in this model, which persisted for at least 4-week post-treatment. This result was associated with modulation of intestinal T helper type 1 cell (Th1) and Th2 cytokine production, and with increased numbers of mesenteric IFN-gamma-producing CD8+ cells.

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    • "The involvement and/or requirement of IFN-γ in immune tolerance was reported by several groups. Tolerance induction to peanut allergens by herbal formula-2 was associated with the upregulation of IFN-γ33 by IFN-γ-producing CD8(+) T cells.34 However, it was unclear whether IFN-γ upregulation was secondary to tolerance acquisition or was the primary cause of the successful induction of food allergen tolerance. "
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    ABSTRACT: Specific oral immunotherapy (SOIT) using interferon-γ (IFN-γ) has been successful as a food allergy treatment. Interleukin-10 (IL-10)-producing regulatory B cells (Br1s) play a role in immune tolerance to food allergens. In addition, IFN-γ shows tolerogenic effects on allergen-induced Br1 responses. Eleven patients that were allergic to cow's milk and 12 milk-tolerant subjects were selected by double-blind placebo-controlled food challenge (DBPCFC) and clinical characteristics. The immunomodulatory effects of IFN-γ on allergen-specific Br1 responses were evaluated in 6 milk allergy patients and 8 milk-tolerant subjects. Peripheral blood mononuclear cells (PBMCs) from subjects were stimulated with casein and/or IFN-γ and analyzed by flow cytometry. IFN-γ had no effect on total cell counts or the proportion of Br1 cells in PBMCs. IFN-γ stimulation did not change total Br1 cell counts or the percentage of Br1s among CD5(+) B cells in the milk allergy or the milk-tolerant groups. In the milk allergy group, Br1 counts were not different between the control and the casein stimulation but significantly increased in the IFN-γ + casein stimulated cells, and the Br1 fractions were decreased after casein stimulation and recovered in the addition of IFN-γ for stimulation. In the milk-tolerant group, Br1 counts increased in the casein stimulated cells and in the IFN-γ + casein stimulated cells, but the increase was significantly less when IFN-γ was added, and the Br1 fractions were increased after casein stimulation and IFN-γ + casein stimulation, that was not significant when IFN-γ was added. IFN-γ-induced allergen-specific Br1 responses in the PBMCs of milk allergy patients play a role in milk allergen-specific tolerance induction in vitro. Further investigations into the molecular immunological mechanisms underlying the induction of allergen-specific Br1 responses are needed.
    Full-text · Article · Jan 2013 · Allergy, asthma & immunology research
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    • "Research suggests that certain Chinese medicinal herbs may have the potential for treating allergy and asthma [6]. For the first time, our group developed a food allergy herbal formula (FAHF2) that blocks peanut-induced anaphylaxis in a mouse model [7,8]. A recent clinical trial demonstrated that the FAHF2 is safe and well-tolerated, with beneficial immunomodulatory effects in vitro [9]. "
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    ABSTRACT: ABSTRACT: Peanut allergy is characterized by increased levels of peanut-specific IgE in the serum of most patients. Thus, the most logical therapy would be to inhibit the IgE production by committed B-cells. This study aims to investigate the unreported anti-IgE effects of Chinese herbal extracts of Rubia cordifolia (Qiancao) and Dianthus superbus (Qumai). Seventy herbal extracts were tested for their ability to reduce IgE secretion by a human B-cell line. Those with the lowest inhibitory concentration 50 (IC50) values were tested in a mouse model of peanut-anaphylaxis. Anaphylactic scores, body temperature, plasma histamine and peanut-specific-immunoglobulins were determined. Rubia cordifolia and Dianthus superbus inhibited the in vitro IgE production by a human B-cell line in a dose-dependent manner and the in vivo IgE production in a murine model of peanut allergy without affecting peanut-specific-IgG1 levels. After challenge, all mice in the sham groups developed anaphylactic reactions and increased plasma histamine levels. The extract-treated mice demonstrated significantly reduced peanut-triggered anaphylactic reactions and plasma histamine levels. The extracts of Rubia cordifolia and Dianthus superbus inhibited the IgE production in vivo and in vitro as well as reduced anaphylactic reactions in peanut-allergic mice, suggesting potentials for allergy treatments.
    Full-text · Article · Sep 2011 · Chinese Medicine
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    • "IgE levels were significantly reduced by FAHF-2 treatment and remained significantly lower as long as 5 weeks posttherapy[42]. In a follow up study, C3H/HeJ mice previously sensitized to peanut were treated with 7 weeks of FAHF-2 or sham treatment[43]. Mice were subsequently challenged 1 day posttherapy and 4 weeks posttherapy. "
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    ABSTRACT: Food allergy poses a significant burden on patients, families, health care providers, and the medical system. The increased prevalence of food allergy has brought about investigation as to its cause and new treatments. Currently, the only treatment available is to avoid the food and symptomatically treat any reactions. There are multiple clinical and murine models of food allergy treatment that use allergen specific and nonspecific pathways. Allergen specific treatments use mucosal antigen exposure as a method of inducing desensitization and tolerance. Allergen nonspecific methods act via a more global TH2 suppressive mechanism and may be useful for those patients with multiple food allergies.
    Full-text · Article · Dec 2009 · World Allergy Organization Journal
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