Original article Topical glucocorticoids downregulate COX-1 positive cells in nasal polyps Nasal polyposis is a multifactorial disease, associated with asthma, primary ciliary dyskinesia, acetyl salicylic acid (ASA) intolerance and possibly allergy, affecting between 1% and 4% of the general population (1, 2). Although many hypotheses have been suggested, the pathogenesis of nasal polyposis is still largely unknown. Macroscopically, nasal polyps are characterized by the presence of edematous masses of inflamed mucosa that are predominantly localized in the middle meatus and prolaps into the nose, leading to nasal obstruction, secretion, loss of smell, headache/facial pain, and reduced quality of life (3, 4). Histologically, nasal polyps are characterized by a cover of respiratory epithelium, large quantities of extracellular oedema and a dense inflam- matory cell infiltrate consisting of mast cells, eosinophils, lymphocytes, neutrophils and plasma cells, that release a variety of pro-inflammatory mediators, including cyto- kines, histamine, prostanoids and leukotrienes [for review see Fokkens et al. (3)]. In recent years, various randomized controlled trials have demonstrated the effectiveness of topical glucocor- ticoids (GC) in the treatment of primary and recurrent nasal polyposis (5–13). However, the mechanisms underlying the anti-inflammatory and immunoregulatory effects of these drugs in vivo remain to be fully explained. GC are known to exhibit anti-edematous and strong anti-inflammatory effects that are in part attributed to their interference with prostanoid synthesis (14). Cyclo- oxygenases are key enzymes in the generation of prosta- noids from arachidonic acid and exist in at least two isoforms: cyclooxygenase-1 (COX-1) and cyclooxygenase- 2 (COX-2). COX-1 is considered to be expressed consti- tutively in all cells, whereas COX-2 is considered to be induced under inflammatory conditions. As both isoforms Background: Influx of inflammatory cells is one of the hallmarks of nasal polyposis. As glucocorticoids (GC) are known to exhibit strong anti-inflam- matory effects, these drugs are frequently used in the treatment of the disease. Part of the anti-inflammatory effects of GC is attributed to their interference with prostanoid synthesis. As cyclooxygenases (COX) are key enzymes in the synthesis of both pro- (COX-1, COX-2) and anti-inflammatory prostanoids (COX-2), we investigated the role of topical GC on COX-1, COX-2 and inflammatory markers in nasal polyps (NP). Methods: Immunohistochemical analysis of inflammatory markers (CD68, CD117, MBP, elastase, IgE, BB-1, IL-4, IL-5 and IL-6), COX-1 and COX-2 was performed on normal nasal mucosa (NM) (n = 18), non-GC treated NP (n = 27) and topical GC treated NP (n = 12). NP groups were matched for allergy, asthma and ASA intolerance. Results: Increased numbers of eosinophils, IL-5+ cells and IgE+ cells and decreased numbers of mastcells are striking features of NP inflammation (P < 0.05). In addition, increased numbers of COX-1+ cells are observed in NP epithelium compared to NM (P < 0.05). Conclusion: Topical GC significantly reduce the number of COX-1+ NP cells (P < 0.05), but have no significant effect on COX-2+ NP cells. No significant reduction in the number of eosinophils is observed for GC treated NP. The number of IL-5+ cells is however increased significantly upon GC treatment (P < 0.05). F. A. Ebbens 1 , M. Maldonado 2 , E. J. J. de Groot 1 , I. Alobid 2 , C. M. van Drunen 1 , C. Picado 3 , W. J. Fokkens 1 , J. Mullol 2 1 Department of Otorhinolaryngology Head & Neck Surgery, Academic Medical Center, Amsterdam, The Netherlands; 2 Rhinology Unit & Smell Clinic, Department of Otorhinolaryngology, Hospital Clinic, IDIBAPS; 3 Department of Pneumology and Respiratory Allergy, Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain Key words: cyclooxygenase-1; cyclooxygenase-2; eosinophils; glucocorticoids; interleukin-5; nasal polyps; topical administration. F. A. Ebbens MD MSc Department of Otorhinolaryngology Head & Neck Surgery Academic Medical Center Meibergdreef 9 1105 AZ Amsterdam the Netherlands Accepted for publication 8 May 2008 Abbreviations: AP, alkaline phosphatase; ASA, acetyl salicylic acid; COX-1, cyclooxygenase-1; COX-2, cyclooxygenase-2; ENT, ear, nose and throat; ESS, endoscopic sinus surgery; GC, glucocortic- oids; NP, nasal polyps; NM, normal nasal mucosa; NSAIDs, nonsteroidal anti-inflammatory drugs; PBS, phosphate-buffered saline. Allergy 2009: 64: 96–103 Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2008.01815.x 96