Original article Inverse relation between nasal fluid Clara Cell Protein 16 levels and symptoms and signs of rhinitis in allergen-challenged patients with intermittent allergic rhinitis Decreased expression of the anti-inflammatory gene Clara Cell Protein 16 (CC16) may contribute to allergic inflammation. This protein, which is also known as CC16 or uteroglobin is secreted by Clara cells in the lungs and by nasal mucosal epithelial cells. Clara Cell Protein 16 has important anti-inflammatory effects, such as the inhibi- tion of leukocyte chemotaxis, proinflammatory cytokines, and protease activity (1). The relevance of CC16 to allergic disease is supported by several observations. Peptides derived from CC16 have been found to be effective in an animal model of allergic conjunctivitis (2). Decreased levels of CC16 have been described in inter- mittent allergic rhinitis (IAR) and asthma (3–8). In asthma low CC16 has been associated with airway hyperreactivity. However, in IAR the association between CC16 and clinical disease severity is less clear. Lower nasal fluid CC16 levels in symptomatic patients with IAR than in healthy controls support that CC16 could have a role in the disease (7). However, in one study CC16 concentrations were generally low, both before and during season as well as following treatment with glucocorticoids (8). This makes the relation between CC16 and disease severity less clear. A possible explan- ation for this could be a primary genetic cause. The CC16 gene is located on chromosome 11q12-13. This region is linked to atopy and contains candidate genes for allergy such as the high-affinity immunoglobulin E receptor. An adenine (A) to guanine (G) substitution in the promoter region of the gene-encoding CC16 (A38G) has been associated with low expression of CC16 and airway hyperreactivity in asthma (6, 9–11). However, the association with this single nucleotide polymorphism (SNP) could not be replicated in other studies of asthma (12, 13). The A38G SNP has not been examined IAR. An alternative explanation for altered CC16 production in allergy could be that proinflammatory cytokines, such as tumor necrosis factor-a (14–16) regulate CC16 synthesis. As CC16 itself affects cytokine production, it is possible that the balance between the two constitutes a regulatory mechanism in mucosal inflammation. The relation between CC16 and clinical disease can be readily studied in IAR. Signs of rhinitis can be determined Background: Decreased levels of the anti-inflammatory Clara Cell Protein 16 (CC16) are found in intermittent allergic rhinitis (IAR) and asthma. In asthma this decrease has been associated with hyperreactivity and the A38G single nucleotide polymorphism (SNP). The aim of this study was to examine if IAR is associated with signs and symptoms of rhinitis and the A38G SNP. Methods: Nasal fluid CC16 was analyzed in 20 patients with IAR before allergen challenge and 1 and 6 h after challenge, and from 28 healthy controls. The A38G SNP was analyzed in 80 patients with IAR and 106 controls. Nasal biopsies were obtained from three subjects in each group for immunohistochemical analysis of CC16. Results: In the allergen-challenged patients symptoms and rhinoscopic signs of rhinitis increased after 1 h and normalized after 6 h. In contrast, nasal fluid CC16 decreased 1 h after allergen challenge and returned to baseline after 6 h. Nasal fluid CC16 levels did not differ from controls before and 6 h after chal- lenge. Immunohistochemical investigation showed intense CC16 staining in the nasal epithelium of both patients before season and healthy controls, but weak staining in symptomatic patients during season. No significant association be- tween the A38G SNP and IAR was found. Conclusion: There was an inverse relation between nasal fluid CC16 levels and symptoms and signs of rhinitis in allergen-challenged patients with IAR. How- ever, there was no association between IAR and the A38G SNP. M. Benson 1 , M. Fransson 2 , T. Martinsson 3 , . T. Naluai 3 , R. Uddman 2 , L. O. Cardell 2 1 Queen Silvia Children's Hospital, Gothenburg; 2 Laboratory for Clinical and Experimental Allergy Research, Department of Oto-Rhino-Laryngology, Malmç University Hospital, Malmç; 3 Department of Clinical Genetics, Gothenburg, Sweden Key words: allergic rhinitis; Clara Cell Protein 16; nasal fluid. Mikael Benson Queen Silvia Children's Hospital SE-416 85 Gothenburg Sweden Accepted for publication 26 September 2006 Allergy 2007: 62: 178–183 Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2006.01264.x 178