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.