Original article Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine Antihistamines are widely regarded as effective treatment of various allergic conditions including allergic rhinitis and chronic urticaria (1). Their clinical efficacy seems to be directly related to H1 receptor inhibition with subse- quent abrogation of effects of histamine released during allergic reactions from mast cells and basophils (2). Studies published over last two decades demonstrated that most second generation antihistamines in addition to the H1 receptor-mediated effects also can produce a significant influence on inflammatory cell activity in vitro (2). Desloratadine (DL) the primary active metabolite of loratadine is a potent H1 receptor antagonist (3). Desl- oratadine can inhibit release of mediators from isolated mast cells and basophils (4–6) down-regulate cytokine expression in human nasal epithelial cells (7), inhibit adhesion molecule expression on epithelial cells (8) and activation of endothelial cells (9). The relevance of the in vitro antiallergic activity of antihistamines to their clinical effectiveness in vivo is not clear since antihista- mines are active in vitro typically at micromolar concen- trations, especially with respect to histamine and leukotriene release inhibition, thus requiring concentra- tions which are greater than serum concentrations which are nanomolar. However, it is possible that antihistamines may accumulate at the site of inflammation achieving locally a greater concentration than seen in serum. The cellular composition and mediator content of nasal polyp tissue is similar to the inflamed airway mucosa (10). It contains not only mast cells and eosinophils, but also other cells such as mononuclear cells, neutrophils, epithe- lial cells and fibroblasts that are able to modulate activation of effector cells. Accessibility of nasal polyp tissue allows for easy assessment of cells derived from a site of inflammatory reactions, which also accounts for inter- acting between different cell types similar to the situation occurring in vivo. Utilization of dispersed nasal polyp cell preparations allows unique opportunities to assess indi- vidual features of the inflamed tissue such as the degree of eosinophilia and assess the impact of characteristics of patient disease such as clinical severity, which may affect responses to the compound tested. Some patients with nasal polyps suffer from aspirin acetylosalitic acid (ASA)- sensitivity, which is associated with particularly severe rhinosinusitis/asthma recurrent nasal polyposis and prom- inent tissue eosinophilia (11, 12). Chronic inflammation in ASA-sensitive patients is difficult to manage and often resistant to standard treatment with topical glucocortico- steroids (13). Nasal polyp tissue which contains mast cells and eosinophils is similar to the inflamed airway mucosa in cellular composition and mediator content. This investigation assessed the effect of desloratadine (DL), on activation of cells in nasal polyp tissue. Polyps were obtained from 22 patients with chronic rhino- sinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA-tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and incu- bated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC 4 , eosino- phil cationic protein (ECP) and tryptase concentrations in supernatants were measured by immunoassays. Desloratadine (1, 10 and 50 lM) inhibited calcium ionophore-induced LTC 4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE-induced LTC 4 release by a mean of 27%, 35% and 39% respect- ively. Calcium ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 lM of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47% and 66% for 1, 10 and 50 lM of DL. Desloratadine 10 lM and 50 lM inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA-sensitive patients when compared with ASA-tolerant patients released at baseline significantly more ECP (medians 120.0 lg/ml, range: 69.0– 182.0 vs 63.4 lg/ml, range: 3.7–172.0; P < 0.05), but similar amounts of tryp- tase and LTC 4 . This study demonstrated that DL inhibits activation of both eosinophils and mast cells derived from a site of airway mucosal inflammation. M. L. Kowalski 1 , A. Lewandowska 1 , J. Wozniak 1 , J. Makowska 1 , A. Jankowski 2 , L. DuBuske 3 1 Department of Clinical Immunology and Allergy, Faculty of Medicine, Medical University, Lodz, Poland; 2 ENT Department, Medical University, Lodz, Poland; 3 Immunology Research Institute of New England, Fitchburg, MA, USA Key words: antihistamine; aspirin sensitivity; desloratadine; eosinophils; mast cells; nasal polyps. Professor Marek L. Kowalski Department of Clinical Immunology and Allergy Medical University of Lodz 251 Pomorska Str. 92-213 Lodz Poland Accepted for publication 4 May 2004 Allergy 2005: 60: 80–85 Copyright Ó Blackwell Munksgaard 2005 ALLERGY DOI: 10.1111/j.1398-9995.2005.00642.x 80