title: Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival.
abstract: BACKGROUND
  Herbal medicines have unique odors, and the act of smelling may have modulatory effects on the immune system. We investigated the effect of olfactory exposure to Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, on alloimmune responses in a murine model of cardiac allograft transplantation.
  
  
  METHODS
  Naïve or olfactory-dysfunctional CBA mice underwent transplantation of a C57BL/6 heart and were exposed to the odor of TJ-23 until rejection. Some naïve CBA recipients of an allograft were given olfactory exposure to Sairei-to (TJ-114), trimethylthiazoline (TMT), individual components of TJ-23, or a TJ-23 preparation lacking one component. Adoptive transfer studies were performed to determine whether regulatory cells were generated.
  
  
  RESULTS
  Untreated CBA mice rejected their C57BL/6 allografts acutely, as did olfactory-dysfunctional CBA mice exposed to the odor of TJ-23. CBA recipients of a C57BL/6 heart given olfactory exposure to TJ-23 had significantly prolonged allograft survival, whereas those exposed to the odor of TJ-114, TMT, one component of TJ-23, or TJ-23 lacking a component did not. Secondary allograft recipients that were given, at 30 days after transplantation, either whole splenocytes, CD4+ cells, or CD4+CD25+ cells from primary recipients exposed to the odor of TJ-23 had indefinitely prolonged allograft survival.
  
  
  CONCLUSIONS
  Prolonged survival of cardiac allografts and generation of regulatory cells was associated with exposure to the odor of TJ-23 in our model. The olfactory area of the brain may have a role in the modulation of immune responses.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Jin
authors.forename: Masateru
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. mniimi@zaf.att.ne.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Niimi
mesh_terms: D064591:Allografts; D000818:Animals; D019341:Aromatherapy / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation; D007111:Immunity, Cellular / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009812:Odorants; D010946:Plants, Medicinal; D012903:Smell / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
chemical_list: D004365:Drugs, Chinese Herbal; C413220:toki-shakuyaku-san