Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-10T12:52:30.814Z Has data issue: false hasContentIssue false

Effect of long-term, low-dose clarithromycin on T helper 2 cytokines, eosinophilic cationic protein and the ‘regulated on activation, normal T cell expressed and secreted’ chemokine in the nasal secretions of patients with nasal polyposis

Published online by Cambridge University Press:  04 May 2012

A Perić*
Affiliation:
Rhinology Unit, Department of Otorhinolaryngology, Military Medical Academy, Belgrade, Serbia
D Vojvodić
Affiliation:
Division of Clinical Immunology, Institute of Medical Research, Military Medical Academy, Belgrade, Serbia
S Matković-Jožin
Affiliation:
Department of Ear, Nose and Throat, Innland Hospital, Elverum, Norway
*
Address for correspondence: Dr Aleksandar Perić, Rhinology Unit, Department of Otorhinolaryngology, Military Medical Academy, Crnotravska 17, 11040 Belgrade, Serbia E-mail: alexneta@sezampro.rs

Abstract

Background:

Little is known about the effects of macrolides on the cytokines and chemokines that modulate the function of eosinophils in nasal polyposis.

Methods:

Twenty-two non-allergic and 18 allergic patients with nasal polyps were administered clarithromycin 500 mg/day (single oral dose) for eight weeks. We measured the nasal secretion levels of the T helper 2 (also known as Th2) cytokines interleukin 4, 5 and 6, the ‘regulated on activation, normal T cell expressed and secreted’ (also known as RANTES) chemokine, and the eosinophilic cationic protein, before and after treatment.

Results:

After clarithromycin treatment, we found reduced levels of the ‘regulated on activation, normal T cell expressed and secreted’ chemokine in samples from both non-allergic and allergic patients (p < 0.05). Clarithromycin treatment decreased the levels of eosinophilic cationic protein only in non-allergic patients (p < 0.05), and decreased the level of interleukin 6 only in allergic patients (p < 0.05). Decreased levels of the ‘regulated on activation, normal T cell expressed and secreted’ chemokine were associated with a reduction in polyp size both in non-allergic and allergic patients.

Conclusion:

Clarithromycin has a strong anti-inflammatory effect in nasal polyposis, but has different immunomodulatory effects in allergic and non-allergic nasal polyposis patients.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Ichimura, K, Shimazaki, Y, Ishibashi, T, Higo, R. Effect of new macrolide roxithromycin upon nasal polyps associated with chronic sinusitis. Auris Nasus Larynx 1996;23:4856CrossRefGoogle ScholarPubMed
2Yamada, T, Fujieda, S, Mori, S, Yamamoto, H, Saito, H. Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal lavage. Am J Rhinol 2000;14:143–8CrossRefGoogle ScholarPubMed
3Cervin, A, Wallwork, B. Macrolide therapy of chronic rhinosinusitis. Rhinology 2007;45:259–67Google ScholarPubMed
4Rhee, CS, Majima, Y, Arima, S, Jung, HW, Jinn, TH, Min, YG et al. Effects of clarithromycin on rheological properties of nasal mucus in patients with chronic sinusitis. Ann Otol Rhinol Laryngol 2000;109:484–7Google ScholarPubMed
5Nonaka, M, Pawankar, R, Saji, F, Yagi, T. Effect of roxithromycin on IL-8 synthesis and proliferation of nasal polyp fibroblasts. Acta Otolaryngol Suppl 1998;539:71–5Google ScholarPubMed
6Miyanohara, T, Ushikai, M, Matsune, S, Ueno, K, Katahira, S, Kurono, Y. Effects of clarithromycin on cultured human nasal epithelial cells and fibroblasts. Laryngoscope 2000;110:126–31CrossRefGoogle Scholar
7Pawankar, R. Nasal polyposis: an update. Curr Opin Allergy Clin Immunol 2003;3:16CrossRefGoogle ScholarPubMed
8Bachert, C, Gevaert, P, Holtappels, G, Van Cauwenberge, P. Mediators in nasal polyposis. Curr Allergy Asthma Rep 2002;2:481–7CrossRefGoogle ScholarPubMed
9Nonaka, M, Pawankar, R, Saji, F, Yagi, T. Distinct expression of RANTES and GM-CSF by lipopolysaccharide in human nasal fibroblasts but not in other airway fibroblasts. Int Arch Allergy Immunol 1999;119:314–21CrossRefGoogle Scholar
10Meyer, JE, Bartels, J, Görögh, T, Sticherling, M, Rudack, C, Ross, DA et al. The role of RANTES in nasal polyposis. Am J Rhinol 2005;19:1520CrossRefGoogle ScholarPubMed
11Saji, F, Nonaka, M, Pawankar, R. Expression of RANTES by IL-1β and TNF-α stimulated nasal polyp fibroblasts. Auris Nasus Larynx 2000;27:247–52CrossRefGoogle Scholar
12Fokkens, W, Lund, V, Mullol, J, European Position Paper on Rhinosinusitis and Nasal Polyps Group. European position paper on rhinosinusitis and nasal polyps 2007. Rhinology (suppl) 2007;45:1136Google ScholarPubMed
13Bachert, C, Van Kempen, M, Van Cauwenberge, P. Regulation of proinflammatory cytokines in seasonal allergic rhinitis. Int Arch Allergy Immunol 1999;118:375–9CrossRefGoogle ScholarPubMed
14Perić, A, Vojvodić, D, Radulović, V, Vukomanović-Đurđević, B, Miljanović, O. Correlation between cytokine levels in nasal fluid and eosinophil counts in nasal polyp tissue in asthmatic and nonasthmatic patients. Allergol Immunopathol (Madr) 2011;39:133–9CrossRefGoogle Scholar
15Tsicopoulos, 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;113:462–9CrossRefGoogle ScholarPubMed
16Lildholdt, T, Rundcrantz, H, Bende, M, Larsen, K. Glucocorticoid treatment for nasal polyps: the use of topical budesonide powder, intramuscular betamethasone, and surgical treatment. Arch Otolaryngol Head Neck Surg 1997;123:595600CrossRefGoogle ScholarPubMed
17Pácová, H, Kučera, T, Astl, J, Martínek, J. Detection of beta-defensins and NOS in healthy and pathological nasal mucosa. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2004;148:239–40CrossRefGoogle ScholarPubMed
18Norlander, T, Brönnegård, M, Stierna, P. The relationship of nasal polyps, infection, and inflammation. Am J Rhinol 1999;13:349–55CrossRefGoogle ScholarPubMed
19Fundová, P, Filipovský, T, Funda, DP, Hovorka, O, Holý, R, Navara, M et al. Expression of IGF-1R and iNOS in nasal polyps; epithelial cell homeostasis and innate immune mechanisms in pathogenesis of nasal polyposis. Folia Microbiol 2008;53:558–62CrossRefGoogle ScholarPubMed
20Lo, S, Di Palma, S, George, E, McCombe, AW. Immunolocalisation of heme oxygenase isoforms in human nasal polyps. J Laryngol Otol 2009;123:131–5CrossRefGoogle ScholarPubMed
21Bonfils, P, Badoual, C, Bonfils, NA, Gallast, D, Malinvaud, D. Eosinophil infiltration of nasal polyps in patients with nasal polyposis: role of clinical evaluation after medical and surgical treatment. J Laryngol Otol 2009;123:509–16CrossRefGoogle ScholarPubMed
22Cervin, A, Kalm, O, Sandkull, P, Lindberg, S. One-year low-dose erythromycin treatment of persistent chronic sinusitis after sinus surgery: clinical outcome and effects on mucoliliary parameters and nasal nitric oxide. Otolaryngol Head Neck Surg 2002;126:481–9CrossRefGoogle Scholar
23Haruna, S, Shimada, C, Ozawa, M, Fukami, S, Moriyama, H. A study of poor responders for long-term, low-dose macrolide administration for chronic rhinosinusitis. Rhinology 2009;47:6671Google Scholar
24Nonaka, M, Pawankar, R, Tomiyama, S, Yagi, T. A macrolide antibiotic, roxithromycin, inhibits the growth of nasal polyp fibroblasts. Am J Rhinol 1999;13:267–72CrossRefGoogle ScholarPubMed
25Park, HH, Park, IH, Cho, JS, Lee, YM, Lee, HM. The effect of macrolides on myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts. Am J Rhinol Allergy 2010;24:348–53CrossRefGoogle ScholarPubMed
26Bartels, J, Maune, S, Meyer, JE, Kulke, R, Schlüter, C, Röwert, J et al. Increased eotaxin-mRNA expression in non-atopic and atopic nasal polyps: comparison to RANTES and MCP-3 expression. Rhinology 1997;35:171–4Google ScholarPubMed
27Suzaki, H, Asano, K, Yu, M, Hisamitsu, T. Influence of roxithromycin on inflammatory cytokine production from nasal polyp fibroblasts in vitro. Acta Otolaryngol 2003;123:637–42CrossRefGoogle ScholarPubMed
28Cervin, A, Wallwork, B, Mackay-Sim, A, Coman, WB, Greiff, L. Effects of long-term clarithromycin treatment on nasal lavage fluid markers of inflammation in chronic rhinosinusitis. Clin Physiol Funct Imaging 2009;29:136–42CrossRefGoogle Scholar
29Bachert, 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;53:213CrossRefGoogle ScholarPubMed
30Fan, GK, Wang, H, Takenaka, H. Eosinophil infiltration and activation in nasal polyposis. Acta Otolaryngol 2007;127:521–6CrossRefGoogle ScholarPubMed
31Liu, 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;128:945–51CrossRefGoogle ScholarPubMed