title: Ketotifen induced inhibition of histamine release in a non-IgE model of middle ear effusion.
abstract: The inhibitory effects of ketotifen, a histamine H1-receptor antagonist and mast cell stabilizer, were examined on a non-IgE experimental model of middle ear effusion. Thirty rats were divided into three groups. Group A (n = 9) was subjected to mechanical stimulation of the external auditory canal (EAC); group B (n = 11) was pre-treated with intraperitoneal administration of 0.2 mg ketotifen, 90 min before mechanical stimulation of the EAC; and group C (n = 10), the control group, was neither exposed to mechanical stimulation nor given ketotifen. Thirty minutes after completion of the experiment, the eardrums were inspected, histamine levels were determined by a fluorometric assay, and the pars flaccida underwent histological assessment. An attic effusion was observed in group A; a similar phenomenon but to a lesser extent was also seen in group B. Statistical analysis confirmed that the mean histamine concentration of the rinsing fluid obtained from group A was significantly higher than that of group C (p = 0.004) or group B (p = 0.008). No significant difference was found between the mean histamine concentration of groups C and group B (p = 0.311). Histological assessment revealed that the thickness of the pars flaccida of group A was considerably greater than that of groups C and B and was characterized by marked edema. Furthermore, the pars flaccida mast cell population was significantly depleted compared with groups C and B. The data indicate that mechanical stimulation of the EAC triggered the pars flaccida mast cells to degranulate in a non-mediated IgE fashion and that histamine is implicated in most of these histological changes. It is concluded that administration of ketotifen before mechanical stimulation of the EAC had a stabilizing effect and abolished mast cell degranulation, therefore, may be considered as a potential therapeutic agent for the treatment of middle ear disease in the pediatric population.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Meir Medical Center, Kfar Saba 44281, Israel. berger45@netvision.net.il
authors.forename: Gilead
authors.initials: G
authors.lastname: Berger
authors.forename: Rachel
authors.initials: R
authors.lastname: Berger
authors.forename: Arnon
authors.initials: A
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D004195:Disease Models, Animal; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006636:Histamine Release / Q000187:drug effects*; D007665:Ketotifen / Q000627:therapeutic use*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D010034:Otitis Media with Effusion / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006634:Histamine H1 Antagonists; D007665:Ketotifen