H1 antihistamines are also known to have anti-inflammatory properties. Some studies show that H1 antihistamines prevent histamine release, which is actually independent of the ability to bind H1 receptors. This effect is thought to occur by interfering with calcium activity on the cell membrane, which may be important in signaling to a cell to release histamine. However, other studies say the amount by which histamine release is reduced is not significant clinically.
H1 antihistamines have also been observed to reduce eosinophil accumulation near allergic sites. This may be due to the ability of H1 antihistamines to interfere with activation of a molecule called NF-kB. This molecule is important in production of inflammatory cytokines. NF-kB can be activated by several inflammatory molecules, including histamine and TNF. Low concentrations of cetirizine and azelastine have been shown to result in lower levels of NF-kB while also inhibiting the production of IL-1b, IL-6, IL-8, TNF and GM-CSF.
Bradykinin is a mediator released by mast cells that causes inflammation, pain and edema. H1 antihistamines such as chlorpheniramine and cetirizine have been reported to inhibit bradykinin induced formation of hives, which may mean that bradykinin triggers hitamine release, which in turn participates in hive formation. However, in testing, the amount of histamine found in these reactions was minimal. This implies that H1 antihistamines may be able to inhibit bradykinin action in another way. H1 antihistamines have also inhibited weal and flare responses by methacholine and platelet activating factor (PAF).
Church, Diana S., Church, Martin K. Pharmacology of antihistamines. World Allergy Organization Journal 2011, 4 (Suppl 3): S22-S27.
Leurs, R., et al. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clinical and Experimental Allergy 32 (2002): 489-498.