Cytokine Profiles in Nasal Fluid in Patients with Nasal Polyps: A Flow Cytometric Study
Biological markers in nasal fluid provide valuable information on nasal pathophysiology. The aims of this study were to compare the cytokine profiles of nasal fluid in subjects with nasal polyps (NP) and co-morbid asthma and NP patients without asthma and to determine the role of these cytokines in the development of NP. Thirty patients with NP (15 asthmatic and 15 non asthmatic) were included in this prospective study. Nasal secretion samples were collected from nasal cavities of all 30 subjects. The levels of eleven cytokines (TNF-α, TNF-β, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IFN-γ) were measured using flow cytometry. The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher in patients with NP and asthma compared with subjects with NP without asthma. We also found significantly higher levels of IFN-α, IL-4, IL-6 and IL-10 in allergic patients with NP and asthma compared with those without asthma. In nonallergic patients with NP and asthma, the concentrations of TNF-α, IL-5 and IL-6 were significantly higher than in nonallergic patients with NP without asthma. Our results show that the presence of Th2 cytokines, especially IL-5 and IL-6 in patients with NP and asthma is a more prominent feature than in those without asthma that relates to the increased eosinophilic inflammation. We have also found a significant influence of allergy on the cytokine profiles both in asthmatic and nonasthmatic patients.
Král B, Krejsek J, Paráková Z, Kopecký O, Vokurková D, Derner V, et al. Some serum activity markers of air-ways inflammation in difficult-to-control asthma patients. Acta Medica (Hradec Králové) 1997; 40: 61-70.
Fokkens W, Lund V, Mullol J. European Position Paper on Rhinosinusitis and Nasal Polyps group. European position paper on rhinosinusitis and nasal polyps 2007. Rhinol Suppl 2007; 45 (Suppl 20): 1-136.
Erbek SS, Yurtcu E, Erbek S, Atac FB, Sahin FI, Cakmak O. Proinflammatory cytokine single nucleotide polymorphisms in nasal polyposis. Arch Otolaryngol Head Neck Surg 2007; 133: 705-9.
Carpagnano GE, Resta O, Gelardi M, Spanevello A, Di Gioia G, Giliberti T, et al. Exhaled inflammatory markers in aspirin-induced asthma syndrome. Am J Rhinol 2007; 21: 542-7.
Ramanathan M, Lee WK, Spannhake EW, Lane AP. Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells. Am J Rhinol 2008; 22: 115-21.
Jankowski R, Persoons M, Foliguet B, Coffinet L, Thomas C, Verient-Montaut B. Eosinophil count in nasal secretions of subjects with and without nasal symptoms. Rhinology 2000; 38: 23-32.
Riechelmann H, Deutschle T, Rozsasi A, Keck T, Polzehl D, Büner H. Nasal biomarker profiles in acute and chronic rhinosinusitis. Clin Exp Allergy 2005; 35: 1186-91.
Riechelmann H, Deutschle T, Friemel E, Gross HJ, Bachem M. Biological markers in nasal secretions. Eur Respir J 2003; 21: 600-5.
Bousquet J. Global Initiative for Asthma (GINA) and its objectives. Clin Exp Allergy 2000; 30(Suppl 1): 2-5.
Tsicopoulos A, Shimbara A, De Nadai P, Aldewachi O, Lamblin C, Lassalle P, et al. Involvement of IL-9 in the bronchial phenotype of patients with nasal polyposis. J Allergy Clin Immunol 2004; 113: 462-9.
Malm L. Assessment and staging of nasal polyposis. Acta Otolaryngol 1997; 117: 465-7.
Watelet JB, Gevaert P, Holtappels G, Van Cauwenberge P, Bachert C. Collection of nasal secretions for immunological analysis. Eur Arch Otorhinolaryngol 2004; 261: 242-6.
Bachert C, Van Kempen M, Van Cauwenberge P. Regulation of proinflammatory cytokines in seasonal allergic rhinitis. Int Arch Allergy Immunol 1999; 118: 375-9.
Ohkubo K, Masakazu I, Pawankar R, Gotoh M, Yagi T, Okuda M. Mechanisms of IL-6, IL-8 and GM-CSF release in nasal secretions of allergic patients after nasal challenge. Rhinology 1998; 36: 156-61.
Hens G, Hellings PW. The nose: gatekeeper and trigger of bronchial disease. Rhinology 2006; 44: 179-87.
Rinia AB, Kostamo K, Ebbens FA, Van Drunen CM, Fokkens WJ. Nasal polyposis: a cellular-based approach to answering questions. Allergy 2007; 62: 348-58.
Bachert C, Wagenmann M, Rudack C, Höpken K, Hillebrandt M, Wang D, et al. The role of cytokines in infectious sinusitis and nasal polyposis. Allergy 1998; 53: 2-13.
Hamilos DL, Leung DJ, Wood R, Cunningham L, Bean DK, Yasruel Z, et al. Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis. J Allergy Clin Immunol 1995; 96: 537-44.
Liu CM, Hong CY, Shun CT, Hsiao TY, Wang CC, Wang JS, et al. Inducible cyclooxygenase and interleukin-6 gene expression in nasal polyp fibroblasts. Arch Otolaryngol Head Neck Surg 2002; 128: 945-51.
Van Zele T, Gevaert P, Watelet JB, Claeys G, Holtappels G, Claeys C, et al. Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis. J Allergy Clin Immunol 2004; 114: 981-3.
Hellings PW, Hens G, Meyts I, Bullens D, Vanoirbeek J, Gevaert P, et al. Aggravation of bronchial eosinophilia in mice by nasal and bronchial exposure to Staphylococcus aureus enterotoxin B. Clin Exp Allergy 2006; 36: 1063-71.
Xu G, Xia JH, Zhou H, Yu CZ, Zhang Y, Zuo KJ, et al. Interleukin-6 is essential for Staphylococcal exotoxin B-induced T regulatory cell insufficiency in nasal polyps. Clin Exp Allergy 2009; 39: 829-37.
Dellacono FR, Eisma R, Lafreniere D, Leonard G, Kretzer D. Interferon-gamma expression in human nasal polyps. Laryngoscope 1997; 107: 626-30.
Ohori J, Ushikai M, Sun D, Nishimoto K, Sagara Y, Fukuiwa T, et al. TNF-α upregulates VCAM-1 and NF-κB in fibroblasts from nasal polyps. Auris Nasus Larynx 2007; 34: 177-83.
Van Pelt J, Romijn F. Long-term Quality Control of the cytokine α growth factors and cell adhesion molecule arrays at the Randox Evidence Investigator. Journal of Medical Biochemistry 2009; 28: 300-304.