Mechanisms of Antihistamines and Mast Cell Stabilizers in Ocular Allergic Inflammation

Abstract

Mast cells play a central role in allergic reactions and inflammation. Successful anti-allergic therapies have typically targeted mast cell mediators, particularly histamine. Antihistaminic compounds interact with the various histamine receptors found on many cells, whereas other compounds such as disodium cromoglycate, are referred to as mast cell stabilizers, as they inhibit degranulation. Some of the most successful compounds developed recently are dual-action, in that they have both anti-histaminic and mast cell stabilizing activities. Recent trends in pharmaceutical intervention, however, have been focused on the secondary effects of mast cell mediators on epithelial cell adhesion molecule expression and mediator release in the process of allergic inflammation. Since, the ocular mucosa is highly exposed to environmental allergens it is commonly involved in allergic reactions and, as such, has been a useful and accessible model in which to test new therapies in vivo. These ocular allergen provocation studies permit analysis of ocular surface cells and evaluation of tear film mediators. Furthermore, techniques to purify conjunctival mast cells have facilitated the study of the effects of mast cell stabilizing compounds on other mast cell mediators, such as cytokines, and the direct effects of mast cell mediators on epithelial cells in vitro. This review will discuss current understanding of how anti-histamines and mast cell stabilizers work, particularly in the context of molecular mechanisms of ocular allergic inflammation.

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

“…Ketotifen is a second-generation H 1 antagonist that has (in common with some other members of this class) long been observed to have additional ‘mast cell stabilising properties’ [2]. It is interesting to speculate that all the H 1 antagonists that have this additional action may have a secondary pharmacology as PP2A inhibitors and that this could be a useful screen to evaluate this property.…”

“…For this reason, we included these drugs alongside the anti-allergics cromoglycate, nedocromil in our experiments. In one experiment, we also tested ketotifen, a drug unrelated chemically to the cromone structure, but which shares some cromone pharmacology [2].…”

“…Some H 1 antagonists (e.g. ketotifen, azelastine, pemirolast and olopatidine) also appear to share a similar pharmacology (or exhibit cross-tachyphylaxis) with cromoglycate [2]. Most of these drugs are used for the routine treatment of mild to moderate asthma and/or the topical treatment of ocular and other allergic symptoms.…”

Cromoglycate drugs suppress eicosanoid generation in U937 cells by promoting the release of Anx-A1

“…The family also embraces lodoxamide, traxanol and amlexanox as well as some H 1 antagonists such as ketotifen, azelastine, pemirolast and olopatidine, many of which appear to share a similar pharmacology (or exhibit cross-tachyphylaxis) with cromoglycate [32].…”

Anti-allergic effect of a Korean traditional medicine, Biyeom-Tang on mast cells and allergic rhinitis

“…Among the inflammatory mediators released from mast cells, histamine is one of the most potent vasoactive mediators implicated in the acute phase of immediate hypersensitivity [14]. Since PCA is one of the most important in vivo models of immediate hypersensitivity in local allergic reactions, PCA reaction was induced by the injection of IgE and antigen in this study.…”