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Abstract

Chronic rhinosinusitis is an inflammatory disease of the nasal and sinus mucosa. While there are multiple mechanisms by which inflammation takes place, the processes can be classified as eosinophil dominant or neutrophil dominant. Eosinophil dominant inflammation can be associated with allergen exposure and local or systemic IgE production. It is characterized by Th2 cells and IL-5. Neutrophil-dominant inflammation is triggered by mucosal exposure to microorganisms. It is characterized by Th1 and IL-8. Both eosinophils and neutrophils release cellular contents that contribute to tissue damage and inflammation.

Antibiotics have been increasingly investigated for their anti-inflammatory effects. In the setting of chronic rhinosinusitis, macrolide and tetracycline antibiotics have been trialed for their anti-inflammatory properties. The anti-inflammatory mechanisms of macrolides include the downregulation of proinflammatory genes, improvement of mucociliary function, and decreased neutrophil accumulation. Observational studies provide support for a prolonged trial of macrolide therapy when conventional therapies fail, especially in patients with low serum IgE levels. Tetracyclines exert anti-inflammatory effects by decreasing inflammatory factors, decreasing neutrophil chemotaxis, and decreasing IgE production. Tetracyclines were shown in one study to decrease nasal polyp size but without any lasting symptom improvement. More research is required to establish the utility of tetracyclines in chronic rhinosinusitis. Other antibiotics with anti-inflammatory effects are trimethoprim-sulfamethoxazole and dapsone, but neither has been applied to the rhinologic setting at present.

Antibiotics have a promising role in becoming effective adjunct therapy in patients who have refractory chronic rhinosinusitis. With the evidence currently available, macrolides are a reasonable option in patients with challenging disease. More evidence is needed, however, before tetracyclines can be routinely recommended.

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References

  1. Barnes PJ. Pathophysiology of allergic inflammation. Immunol Rev. 2011;242(1):31–50.

    Article  CAS  PubMed  Google Scholar 

  2. Benninger MS, et al. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Neck Surg. 2003;129(3 Suppl):S1–32.

    Article  PubMed  Google Scholar 

  3. Bachert C, et al. Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis – a GALEN study. Allergy. 2009;64(4):520–33.

    Article  CAS  PubMed  Google Scholar 

  4. Harlin SL, et al. A clinical and pathologic study of chronic sinusitis: the role of the eosinophil. J Allergy Clin Immunol. 1988;81(5 Pt 1):867–75.

    Article  CAS  PubMed  Google Scholar 

  5. Rondon C, et al. Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis. J Allergy Clin Immunol. 2007;119(4):899–905.

    Article  CAS  PubMed  Google Scholar 

  6. Carney AS, et al. Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy? Clin Exp Allergy. 2002;32(10):1436–40.

    Article  CAS  PubMed  Google Scholar 

  7. Wedback A, et al. Seasonal non-allergic rhinitis (SNAR)–a new disease entity? A clinical and immunological comparison between SNAR, seasonal allergic rhinitis and persistent non-allergic rhinitis. Rhinology. 2005;43(2):86–92.

    PubMed  Google Scholar 

  8. Powe DG, Bonnin AJ, Jones NS. ‘Entopy’: local allergy paradigm. Clin Exp Allergy. 2010;40(7):987–97.

    Article  CAS  PubMed  Google Scholar 

  9. Van Zele T, et al. Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis. J Allergy Clin Immunol. 2004;114(4):981–3.

    Article  PubMed  Google Scholar 

  10. Krakauer T. Immune response to staphylococcal superantigens. Immunol Res. 1999;20(2):163–73.

    Article  CAS  PubMed  Google Scholar 

  11. Hatipoglu U, Rubinstein I. Anti-inflammatory treatment of chronic rhinosinusitis: a shifting paradigm. Curr Allergy Asthma Rep. 2008;8(2):154–61.

    Article  CAS  PubMed  Google Scholar 

  12. Yoon BN, et al. Induction of interleukin-8 from nasal epithelial cells during bacterial infection: the role of IL-8 for neutrophil recruitment in chronic rhinosinusitis. Mediators Inflamm. 2010;2010:813610.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Yamada T, et al. Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal lavage. Am J Rhinol. 2000;14(3):143–8.

    Article  CAS  PubMed  Google Scholar 

  14. Konstan MW, Davis PB. Pharmacological approaches for the discovery and development of new anti-inflammatory agents for the treatment of cystic fibrosis. Adv Drug Deliv Rev. 2002;54(11):1409–23.

    Article  CAS  PubMed  Google Scholar 

  15. Van Crombruggen K, et al. Pathogenesis of chronic rhinosinusitis: inflammation. J Allergy Clin Immunol. 2011;128(4):728–32.

    Article  PubMed  Google Scholar 

  16. Branton MH, Kopp JB. TGF-beta and fibrosis. Microbes Infect. 1999;1(15):1349–65.

    Article  CAS  PubMed  Google Scholar 

  17. Thomas WW 3rd, et al. Distribution of topical agents to the paranasal sinuses: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3(9):691–703.

    Article  PubMed  Google Scholar 

  18. Dubin MG, et al. American Rhinologic Society member survey on “maximal medical therapy” for chronic rhinosinusitis. Am J Rhinol. 2007;21(4):483–8.

    Article  PubMed  Google Scholar 

  19. Harvey RJ, Wallwork BD, Lund VJ. Anti-inflammatory effects of macrolides: applications in chronic rhinosinusitis. Immunol Allergy Clin North Am. 2009;29(4):689–703.

    Article  PubMed  Google Scholar 

  20. Wallwork B, et al. A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Laryngoscope. 2006;116(2):189–93.

    Article  CAS  PubMed  Google Scholar 

  21. Videler WJ, et al. Lack of efficacy of long-term, low-dose azithromycin in chronic rhinosinusitis: a randomized controlled trial. Allergy. 2011;66(11):1457–68.

    Article  CAS  PubMed  Google Scholar 

  22. Shinkai M, Henke MO, Rubin BK. Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action. Pharmacol Ther. 2008;117(3):393–405.

    Article  CAS  PubMed  Google Scholar 

  23. Cervin A. The anti-inflammatory effect of erythromycin and its derivatives, with special reference to nasal polyposis and chronic sinusitis. Acta Otolaryngol. 2001;121(1):83–92.

    Article  CAS  PubMed  Google Scholar 

  24. MacLeod CM, et al. Anti-inflammatory activity of clarithromycin in adults with chronically inflamed sinus mucosa. Adv Ther. 2001;18(2):75–82.

    Article  CAS  PubMed  Google Scholar 

  25. Suzuki H, et al. Effects of long-term low-dose macrolide administration on neutrophil recruitment and IL-8 in the nasal discharge of chronic sinusitis patients. Tohoku J Exp Med. 1997;182(2):115–24.

    Article  CAS  PubMed  Google Scholar 

  26. Nakano T, et al. Roxithromycin reinforces epithelial defence function in rabbit trachea. Acta Otolaryngol Suppl. 1998;538:233–8.

    CAS  PubMed  Google Scholar 

  27. Sugiura Y, Ohashi Y, Nakai Y. Roxithromycin stimulates the mucociliary activity of the Eustachian tube and modulates neutrophil activity in the healthy guinea pig. Acta Otolaryngol Suppl. 1997;531:34–8.

    Article  CAS  PubMed  Google Scholar 

  28. Ikeda K, Wu D, Takasaka T. Inhibition of acetylcholine-evoked Cl-currents by 14-membered macrolide antibiotics in isolated acinar cells of the guinea pig nasal gland. Am J Respir Cell Mol Biol. 1995;13(4):449–54.

    Article  CAS  PubMed  Google Scholar 

  29. Rhee CS, et al. Effects of clarithromycin on rheological properties of nasal mucus in patients with chronic sinusitis. Ann Otol Rhinol Laryngol. 2000;109(5):484–7.

    Article  CAS  PubMed  Google Scholar 

  30. Aoshiba K, Nagai A, Konno K. Erythromycin shortens neutrophil survival by accelerating apoptosis. Antimicrob Agents Chemother. 1995;39(4):872–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Chin AC, et al. Anti-inflammatory benefits of tilmicosin in calves with Pasteurella haemolytica-infected lungs. Am J Vet Res. 1998;59(6):765–71.

    CAS  PubMed  Google Scholar 

  32. Wang T, Donahoe PK, Zervos AS. Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12. Science. 1994;265(5172):674–6.

    Article  CAS  PubMed  Google Scholar 

  33. Haruna S, et al. A study of poor responders for long-term, low-dose macrolide administration for chronic sinusitis. Rhinology. 2009;47(1):66–71.

    PubMed  Google Scholar 

  34. Song Y, Bai W, Ji W. An empirical study of treating chronic sinusitis with low dose Roxithromycin. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2009;23(8):357–8, 363.

    CAS  PubMed  Google Scholar 

  35. Cervin A, et al. One-year low-dose erythromycin treatment of persistent chronic sinusitis after sinus surgery: clinical outcome and effects on mucociliary parameters and nasal nitric oxide. Otolaryngol Head Neck Surg. 2002;126(5):481–9.

    Article  PubMed  Google Scholar 

  36. Katsuta S, et al. Therapeutic effect of roxithromycin on chronic sinusitis with nasal – polyps clinical, computed tomography, and electron microscopy analysis. Nihon Jibiinkoka Gakkai Kaiho. 2002;105(12):1189–97.

    Article  PubMed  Google Scholar 

  37. Kimura N, et al. Clinical effect of low-dose, long-term roxithromycin chemotherapy in patients with chronic sinusitis. Acta Med Okayama. 1997;51(1):33–7.

    CAS  PubMed  Google Scholar 

  38. Moriyama H, et al. Evaluation of endoscopic sinus surgery for chronic sinusitis: post-operative erythromycin therapy. Rhinology. 1995;33(3):166–70.

    CAS  PubMed  Google Scholar 

  39. Kita H, Takezawa H. Long-term low dose erythromycin and roxithromycin therapy for chronic sinusitis. Practica Otologica Kyoto. 1995;84(Suppl):62–9.

    Google Scholar 

  40. Minami T, Kubo N, Kumazawa H, et al. Long-term low dose roxithromycin therapy for chronic sinusitis. Practica Otologica Kyoto. 1995;88:1229–36.

    Article  Google Scholar 

  41. Hashiba M, Baba S. Efficacy of long-term administration of clarithromycin in the treatment of intractable chronic sinusitis. Acta Otolaryngol Suppl. 1996;525:73–8.

    CAS  PubMed  Google Scholar 

  42. Kikuchi S, Suzaki H, Aoki A, et al. Clinical effect of long-term low-dose erythromycin therapy for chronic sinusitis. Practica Otologica Kyoto. 1991;84:41–7.

    Article  Google Scholar 

  43. Soler ZM, et al. Antimicrobials and chronic rhinosinusitis with or without polyposis in adults: an evidenced-based review with recommendations. Int Forum Allergy Rhinol. 2013;3(1):31–47.

    Article  PubMed  Google Scholar 

  44. Fokkens, WJ, et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012;(23): p. 3 p preceding table of contents, 1–298.

    Google Scholar 

  45. Griffin MO, Ceballos G, Villarreal FJ. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action. Pharmacol Res. 2011;63(2):102–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Spinale FG. Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res. 2002;90(5):520–30.

    Article  CAS  PubMed  Google Scholar 

  47. d’Ortho MP, et al. Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. Eur J Biochem. 1997;250(3):751–7.

    Article  PubMed  Google Scholar 

  48. Peterson JT. Matrix metalloproteinase inhibitor development and the remodeling of drug discovery. Heart Fail Rev. 2004;9(1):63–79.

    Article  CAS  PubMed  Google Scholar 

  49. Rohde LE, et al. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation. 1999;99(23):3063–70.

    Article  CAS  PubMed  Google Scholar 

  50. Stetler-Stevenson WG, Liotta LA, Kleiner Jr DE. Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J. 1993;7(15):1434–41.

    CAS  PubMed  Google Scholar 

  51. D’Agostino P, et al. Tetracycline inhibits the nitric oxide synthase activity induced by endotoxin in cultured murine macrophages. Eur J Pharmacol. 1998;346(2–3):283–90.

    Article  PubMed  Google Scholar 

  52. Esterly NB, Furey NL, Flanagan LE. The effect of antimicrobial agents on leukocyte chemotaxis. J Invest Dermatol. 1978;70(1):51–5.

    Article  CAS  PubMed  Google Scholar 

  53. Elewski BE, et al. In vivo suppression of neutrophil chemotaxis by systemically and topically administered tetracycline. J Am Acad Dermatol. 1983;8(6):807–12.

    Article  CAS  PubMed  Google Scholar 

  54. Joks R, Durkin HG. Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs. Pharmacol Res. 2011;64(6):602–9.

    Article  CAS  PubMed  Google Scholar 

  55. Joks R, et al. Tetracycline-mediated IgE isotype-specific suppression of ongoing human and murine IgE responses in vivo and murine memory IgE responses induced in vitro. Int Immunol. 2010;22(4):281–8.

    Article  CAS  PubMed  Google Scholar 

  56. Kuzin II, et al. Tetracyclines inhibit activated B cell function. Int Immunol. 2001;13(7):921–31.

    Article  CAS  PubMed  Google Scholar 

  57. Sommer JU, et al. In vitro effects of doxycycline on inflammatory cytokines and gelatinases in chronic rhinosinusitis. In Vivo. 2012;26(3):369–74.

    CAS  PubMed  Google Scholar 

  58. Van Zele T, et al. Oral steroids and doxycycline: two different approaches to treat nasal polyps. J Allergy Clin Immunol. 2010;125(5):1069–76.e4.

    Article  PubMed  Google Scholar 

  59. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol. 2006;54(2):258–65.

    Article  PubMed  Google Scholar 

  60. Kloppenburg M, et al. The influence of tetracyclines on T cell activation. Clin Exp Immunol. 1995;102(3):635–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Tilley BC, et al. Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group. Ann Intern Med. 1995;122(2):81–9.

    Article  CAS  PubMed  Google Scholar 

  62. O’Dell JR, et al. Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum. 2001;44(10):2235–41.

    Article  PubMed  Google Scholar 

  63. Ciancio S, Ashley R. Safety and efficacy of sub-antimicrobial-dose doxycycline therapy in patients with adult periodontitis. Adv Dent Res. 1998;12(2):27–31.

    Article  CAS  PubMed  Google Scholar 

  64. Roberts DE, Curd JG. Sulfonamides as antiinflammatory agents in the treatment of Wegener’s granulomatosis. Arthritis Rheum. 1990;33(10):1590–3.

    Article  CAS  PubMed  Google Scholar 

  65. Suematsu M, et al. Sulfasalazine and its metabolites attenuate respiratory burst of leukocytes–a possible mechanism of anti-inflammatory effects. J Clin Lab Immunol. 1987;23(1):31–3.

    CAS  PubMed  Google Scholar 

  66. Stegeman CA, et al. Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med. 1994;120(1):12–7.

    Article  CAS  PubMed  Google Scholar 

  67. White ES, Lynch JP. Pharmacological therapy for Wegener’s granulomatosis. Drugs. 2006;66(9):1209–28.

    Article  CAS  PubMed  Google Scholar 

  68. Grunwald MH, Amichai B. Dapsone - the treatment of infectious and inflammatory diseases in dermatology. Int J Antimicrob Agents. 1996;7(3):187–92.

    Article  CAS  PubMed  Google Scholar 

  69. Chang DJ, et al. Dapsone in rheumatoid arthritis. Semin Arthritis Rheum. 1996;25(6):390–403.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Luke Rudmik MD, MSc .

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Liu, C.C., Smith, T.L., Rudmik, L. (2015). Oral Antibiotics as Anti-inflammatories. In: Batra, P., Han, J. (eds) Practical Medical and Surgical Management of Chronic Rhinosinusitis. Springer, Cham. https://doi.org/10.1007/978-3-319-16724-4_13

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  • DOI: https://doi.org/10.1007/978-3-319-16724-4_13

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