NeuroImmune Transmitters: Histamine

It’s allergy season, and that means antihistamines will be flying off drugstore shelves.  Antihistamines are often one of the first-line therapies used by allergy sufferers.  These histamine receptor antagonists, work by blocking histamine activity and signaling.  Histamine is best known for being released by mast cells during inflammatory responses, especially allergic reactions.  It is known that histamine synthesis and release is influenced by cytokines (IL-1, IL-3, IL-12, IL-18, TNF-α), but histamine’s role in immunoregulation is not completely understood.  Conditions at the cellular level, including receptor types, influence histamine activity on the immune system.  Below is a sampling of the interaction between histamine and immune system activity.

  • O’Mahony et al. (2011) identified some of the effects histamine receptors had on the immune system.  Histamine 1 receptor (H1R) activation, a major player in immediate hypersensitivity, is preceded by upregulation of IL-3, IL-4 and histamine itself.  H2R can antagonize H1R effects and is found in the central nervous system (CNS).  However, too little histamine can result in the downregulation of H2R, leading to poor immune modulation.  H3R, also found in the CNS, is responsible for histamine’s role in the sleep-wake cycle, cognition, and inflammation regulation.  H3R deficiencies result in increased expression of macrophage inflammatory protein 2, IFN-10, and CSCR3 by T cells.  The authors also stress that healthy histamine levels are very important as both excess and deficiency are indicative of immune issues.
  • Elevated histamine levels are associated with functional gastrointestinal (GI) disorders.  An article by Akhavein, et al (2012), found that high levels of histamine were associated with high levels of mast cells found in biopsies of the stomach, small bowel, and colon of individuals presenting with abdominal pain, early satiety, and nocturnal awakening.

Histamine is strongly associated with upregulated immune activity, especially of mast cells.  When you see an imbalance in urinary histamine levels, make sure to consider possible immune issues.

Akhavein, M.A., et al. (2012). Allergic mastocytic gastroenteritis and colitis: an unexplained etiology in chronic abdominal pain and gastrointestinal dysmotility. Gastroenterol Res Pract, Epub ahead of print (March 12).
O’Mahony, L., et al. (2011). Regulation of the immune response and inflammation by histamine and histamine receptors. J Allergy Clin Immunol, 128(6): 1153-62.
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4 Responses to NeuroImmune Transmitters: Histamine

  1. Can you explain how histamine reacts to L-Histidine? Also I believe I read that the hormone estrogen stimulates histamine production. Can you confirm that?

    • Sarah Mo says:

      Histidine is the precursor to histamine. Histamine is synthesized from histidine using the enzyme aromatic amino acid decarboxylase and Vitamin B6 as a cofactor.

      There is some evidence to suggest that estrogen stimulates histamine production. A study by Ohtsuka, et al in 1989 concluded estrogen can stimulate histamine production, resulting in GnRH release, from the medio-basal hypothalamus.

  2. Thank you for the response. What are the effects of a synthetic L-histidine on natural histamine production? I ask this because the HPV vaccine Gardasil contains L-histidine – the only vaccine to have this ingredient. The vaccine has been mandated for girls (and boys) ages 9 to 26. Many are experiencing neuro-endocrine-immune imbalances post-vaccination. I am very familiar with and refer to what NeuroScience Inc. calls the NEI Super System.

    Another question: Is it possible that the over abundance of estrogen in adolescent’s girl’s bodies (genetics, environment, synthetic hormone use and food/water sources) and the resulting increase in histamine production is a possible cause of the rise in autoimmune diseases?

    • Sarah Mo says:

      We would expect synthetic histidine, as long as it is the exact same chemical formulation as natural histidine, to have the same support for histamine production. There is 0.78mg of histidine in a dose of Gardasil, and the WHO recommended daily intake of histidine is 10mg/kg of body weight. Histidine is included in some vaccines to improve pH stability and adjuvant adsorption, and it can reduce antigen hydrolysis.

      In terms of estrogen contributing to the rise in autoimmune disease, none of the studies I have read indicated this being an element to consider. However, that doesn’t preclude it from being a contributing factor. There are also other factors, for example increases in food, environment, and metal allergies, that could also be increasing histamine synthesis.

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