Fox smell abrogates the effect of herbal odor to prolong mouse cardiac allograft survival.

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.

Theoretical accounts of Gulf War Syndrome: from environmental toxins to psychoneuroimmunology and neurodegeneration.

Non-specific illness includes a wide variety of symptoms: behavioural (e.g., reduced food and water intake), cognitive (e.g., memory and concentration problems) and physiological (e.g., fever). This paper reviews evidence suggesting that such symptoms can be explained more parsimoniously as a single symptom cluster than as a set of separate illnesses such as Gulf War Syndrome (GWS) and chronic fatigue syndrome (CFS). This superordinate syndrome could have its biological basis in the activity of pro-inflammatory cytokines (in particular interleukin-1: IL-1), that give rise to what has become known as the 'sickness response'. It is further argued that the persistence of non-specific illness in chronic conditions like GWS may be (in part) attributable to a bio-associative mechanism (Ferguson and Cassaday, 1999). In the case of GWS, physiological challenges could have produced a non-specific sickness response that became associated with smells (e.g., petrol), coincidentally experienced in the Persian Gulf. On returning to the home environment, these same smells would act as associative triggers for the maintenance of (conditioned) sickness responses. Such associative mechanisms could be mediated through the hypothalamus and limbic system via vagal nerve innervation and would provide an explanation for the persistence of a set of symptoms (e.g., fever) that should normally be short lived and self-limiting. We also present evidence that the pattern of symptoms produced by the pro-inflammatory cytokines reflects a shift in immune system functioning towards a (T-helper-1) Th1 profile. This position contrasts with other immunological accounts of GWS that suggest that the immune system demonstrates a shift to a Th2 (allergy) profile. Evidence pertaining to these two contrasting positions is reviewed.

Effects of a long-term inhalation of fragrances on the stress-induced immunosuppression in mice.

The aim of this study was to determine the effects of the long-term application of various fragrances on the suppression of immune response induced by high-pressure stress in mice. The immune response was analyzed based on plaque-forming cell (PFC) count, using mice sensitized with sheep red blood cells. The decreased PFC involving thymic involution induced by high-pressure stress in mice was restored by exposing the stressed mice to tuberose, lemon, oakmoss and labdanum for 24 h following exposure to stress. The decreased PFC and thymic involution from stress were restored by exposure to lemon and oakmoss, but not to tuberose and labdanum when the mice were exposed to those fragrances continuously for 3 weeks before the stress was given, followed by exposure to the same fragrances for 24 h after the stress. The decreased PFC and thymic involution from stress were restored by exposure to lemon and labdanum for 24 h after the stress, but not to tuberose over 3 weeks before the stress was given. These data suggest that the neuroimmunomodulatory effects of fragrances may be affected by tolerance depending on the kinds of fragrances in the case of a long-term application.