title: Induction of tolerance after establishment of peanut allergy by the food allergy herbal formula-2 is associated with up-regulation of interferon-gamma.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors.forename: C
authors.initials: C
authors.lastname: Qu
authors.forename: K
authors.initials: K
authors.lastname: Srivastava
authors.forename: J
authors.initials: J
authors.lastname: Ko
authors.forename: T F
authors.initials: TF
authors.lastname: Zhang
authors.forename: H A
authors.initials: HA
authors.lastname: Sampson
authors.forename: X-M
authors.initials: XM
authors.lastname: Li
mesh_terms: D000707:Anaphylaxis / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D010367:Arachis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000097:blood / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D018928:Immunity, Mucosal / Q000187:drug effects; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D015848:Interleukin-5 / Q000097:blood / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D008643:Mesentery / Q000276:immunology / Q000378:metabolism; D051379:Mice; D021183:Peanut Hypersensitivity / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; C497376:Food Allergy Herbal Formula-2; D015848:Interleukin-5; D010936:Plant Extracts; D015847:Interleukin-4; D006632:Histamine; D007371:Interferon-gamma