Summary
Histamine antagonists together with topical steroids are the treatment of choice in allergic rhinitis. Many of these histamine antagonists exhibit effects in addition to blockade of the histamine receptor. In this study we have investigated the effects of ebastine and carebastine on the release of eicosanoids and cytokines from human dispersed polyp cells and the effect of these compounds on the release of inflammatory mediators into nasal lavage fluid after allergen challenge. Ebastine was shown to block the release of anti-IgE-induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp cells (IC30 values of 2.57 and 9.6 μmol/L, respectively) and to inhibit the release of cytokines. Carebastine inhibited the release of PGD2 (IC30 8.14 μmol/L) but had little effect on cytokine release. When patients underwent nasal provocation tests with allergen, ebastine significantly increased the mean number of pollen grains required to induce an allergic response. In addition, the drug inhibited the release of granulocyte-macrophage colony-stimulating factor but had no effect on any other mediators measured.
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Bousquet J, Lebel B, Chanal I, et al. Antiallergic activity of H1-receptor antagonists assessed by nasal challenge. J Allergy Clin Immunol 1988; 82: 881–7.
Stoop AE, van der Heijden HA, Biewenga J, et al. Eosinophils in nasal polyps and nasal mucosa: an immunohistochemical study. J Allergy Clin Immunol 1993; 91: 616–22.
Linder A, Karlsson-Parra A, Hirvela C, et al. Immunocompetent cells in human nasal polyps and normal mucosa. Rhinology 1993; 31: 125–9.
Ohno I, Lea RG, Flanders KC, et al. Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). J Clin Invest 1992; 89: 1662–8.
Hamilos DL, Leung DY, Wood R, et al. Chronic hyperplastic sinusitis: association of tissue eosinophilia with mRNA expression of granulocyte-macrophage colony-stimulating factor and interleukin-3. J Allergy Clin Immunol 1993; 92: 39–48.
Tos M, Sasaki Y, Ohnishi M, et al. Fireside conference 2. Pathogenesis of nasal polyps. Rhinology 1992; 14 Suppl.: 181–5.
Naclerio RM, Meier HL, Kagey-Sobotka A, et al. In vivo model for the evaluation of topical antiallergic medications. Arch Otolaryngol 1984; 110: 25–7.
Sim TC, Grant JA, Hilsmeier KA, et al. Proinflammatory cytokines in nasal secretions of allergic subjects after antigen challenge. Am J Respir Crit Care Med 1994; 149: 339–44.
Campbell AM, Chanez P, Marty-Ane C, et al. Modulation of eicosanoid and histamine release from human dispersed lung cells by terfenadine. Allergy 1993; 48: 125–9.
Holgate S, Burns G, Robinson C, et al. Anaphylactic and calcium-dependent generation of prostaglandin D2 (PGD2), thromboxane B2 and other cyclo-oxygenase products of arachidonic acid by dispersed lung cells and relationship to histamine release. J Immunol 1984; 133: 2138–44.
Campbell AM, Bousquet J. Anti-allergic activity of H1-blockers. Int Arch Allergy Immunol 1993; 101: 308–10.
Lebel B, Bousquet J, Morel A, et al. Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains. J Allergy Clin Immunol 1988; 82: 869–77.
Anderson M, Nolte H, Buamgarten C, et al. Suppressive effect of loratadine on allergen-induced histamine release in the nose. Allergy 1991; 46: 540–6.
Naclerio RM, Kagey-Sobotka A, Lichtenstein LM, et al. Terfenadine, an H1 antihistamine inhibits histamine release in vivo in the human. Am Rev Respir Dis 1990; 142: 167–71.
Togias AG, Proud D, Kagey-Sobotka A, et al. In vivo and in vitro effects of antihistamines on mast cell mediator release: a potentially important property in the treatment of allergic disease. Ann Allergy 1989; 63: 465–9.
Shin MH, Baroody F, Proud D, et al. The effect of azelastine on the early allergic response. Clin Exp Allergy 1992; 22: 189–95.
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Campbell, A., Michel, FB., Bremard-Oury, C. et al. Overview of Allergic Mechanisms. Drugs 52 (Suppl 1), 15–19 (1996). https://doi.org/10.2165/00003495-199600521-00005
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DOI: https://doi.org/10.2165/00003495-199600521-00005