Mechanisms of antihistamines and mast cell stabilizers in ocular allergic inflammation.
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.
Cook
E B
EB
University of Wisconsin-Madison, School of Medicine, Department of Medicine, WI 53792, USA.
Stahl
J L
JL
Barney
N P
NP
Graziano
F M
FM
D000818:Animals; D005128:Eye Diseases / Q000188:drug therapy* / Q000473:pathology; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000502:physiology; D017455:Receptors, IgE / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D017455:Receptors, IgE