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Macrolide immunomodulation of chronic respiratory diseases

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Abstract

Important immunomodulatory properties of 14-and 15-membered macrolides may benefit patients with respiratory diseases associated with chronic inflammation. These properties include decreased neutrophil chemotaxis and infiltration into the respiratory epithelium, inhibition of transcription factors leading to decreased proinflammatory cytokine production, down-regulation of adhesion molecule expression, inhibition of microbial virulence factors including biofilm formation, reduced generation of oxygen-free radicals, enhanced neutrophil apoptosis, and decreased mucus hypersecretion with improved mucociliary clearance. Chronic, low-dose macrolides have dramatically improved survival in patients with diffuse panbronchiolitis (DPB). Given the overlap in pathogenesis between DPB and other chronic respiratory diseases, macrolides are being investigated for cystic fibrosis, asthma, chronic bronchitis, chronic sinusitis, and chronic obstructive pulmonary disease. Preliminary data (largely from open-label trials) are promising, but conclusive results are needed.

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References and Recommended Reading

  1. Beuther DA, Martin RJ: Antibiotics in asthma. Curr Allergy Asthma Rep 2004, 4:132–138.

    Article  PubMed  Google Scholar 

  2. Kudoh S, Azuma A, Yamamoto M, et al.: Improvement of survival in patients with diffuse panbronchiolitis treated with low-dose erythromycin. Am J Respir Crit Care Med 1998, 157:1829–1832.

    PubMed  CAS  Google Scholar 

  3. Tateda K, Ishii Y, Matsumoto T, et al.: Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin. Antimicrob Agents Chemother 1996, 40:2271–2275.

    PubMed  CAS  Google Scholar 

  4. Mandell LA, Bartlett JG, Dowell SF, et al.: Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003, 37:1405–1433.

    Article  PubMed  Google Scholar 

  5. Amsden GW: Anti-inflammatory effects of macrolidesan underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother 2005, 55:10–21.

    Article  PubMed  CAS  Google Scholar 

  6. Wozniak DJ, Keyser R: Effects of subinhibitory concentrations of macrolide antibiotics on Pseudomonas aeruginosa. Chest 2004, 125(Suppl 2):62S–69S.

    Article  PubMed  CAS  Google Scholar 

  7. Hirakata Y, Kaku M, Mizukane R, et al.: Potential effects of erythromycin on host defense systems and virulence of Pseudomonas aeruginosa. Antimicrob Agents Chemother 1992, 36:1922–1927.

    PubMed  CAS  Google Scholar 

  8. Yanagihara K, Tomono K, Imamura Y, et al.: Effect of clarithromycin on chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation in an experimental murine model. J Antimicrob Chemother 2002, 49:867–870.

    Article  PubMed  CAS  Google Scholar 

  9. Kawamura-Sato K, Iinuma Y, Hasegawa T, et al.: Effect of subinhibitory concentrations of macrolides on expression of flagellin in Pseudomonas aeruginosa and Proteus mirabilis. Antimicrob Agents Chemother 2000, 44:2869–2872.

    Article  PubMed  CAS  Google Scholar 

  10. Cervin A, Wallwork B: Anti-inflammatory effects of macrolide antibiotics in the treatment of chronic rhinosinusitis. Otolaryngol Clin N Amer 2005, 38:1339–1350.

    Article  Google Scholar 

  11. Rubin BK, Druce H, Ramirez OE, et al.: Effect of clarithromycin on nasal mucus properties in healthy subjects and in patients with purulent rhinitis. Am J Respir Crit Care Med 1997, 155:2018–2023.

    PubMed  CAS  Google Scholar 

  12. Shinkai M, Rubin BK: Macrolides and airway inflammation in children. Paed Resp Rev 2005, 6:227–235.

    Article  Google Scholar 

  13. Tamaoki J: The effects of macrolides on inflammatory cells. Chest 2004, 125(Suppl 2):41S–51S.

    Article  PubMed  CAS  Google Scholar 

  14. Tamaoki J, Kadota J, Takizawa H: Clinical implications of the immunomodulatory effects of macrolides. Am J Med 2004, 117(Suppl 9A):5S–11S.

    PubMed  CAS  Google Scholar 

  15. Labro MT, Abdelghaffar H: Immunomodulation by macrolide antibiotics. J Chemother 2001, 13:3–8.

    PubMed  CAS  Google Scholar 

  16. Kikuchi T, Hagiwara K, Honda Y, et al.: Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by human monocytes through AP-1 and NF-kappaB transcription factors. J Antimicrob Chemother 2002, 49:745–755.

    Article  PubMed  CAS  Google Scholar 

  17. Schultz MJ: Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis. J Antimrob Chemother 2004, 54:21–28.

    Article  CAS  Google Scholar 

  18. Yamaryo T, Oishi K, Yoshimine H, et al.: Fourteen-member macrolides promote the phosphatidylserine receptor-dependent phagocytosis of apoptotic neutrophils by alveolar macrophages. Antimicrob Agents Chemother 2003, 47:48–53.

    Article  PubMed  CAS  Google Scholar 

  19. Kudoh S: Applying lessons learned in the treatment of diffuse panbronchiolitis to other chronic inflammatory diseases. Am J Med 2004, 117(Suppl 9A):12S–19S.

    PubMed  CAS  Google Scholar 

  20. Tamaoki J, Takeyama K, Tagaya E, et al.: Effect of clarithromycin on sputum production and its rheological properties in chronic respiratory tract infections. Antimicrob Agents Chemother 1995, 39:1688–1690.

    PubMed  CAS  Google Scholar 

  21. Ferrara G, Losi M, Franco F, et al.: Macrolides in the treatment of asthma and cystic fibrosis. Respir Med 2005, 99:1–10.

    Article  PubMed  CAS  Google Scholar 

  22. Wolter J, Seeney S, Bell S, et al.: Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomized trial. Thorax 2002, 57:212–216.

    Article  PubMed  CAS  Google Scholar 

  23. Equi A, Balfour-Lynn IM, Bush A, et al.: Long term azithromycin in children with cystic fibrosis: a randomized, placebo-controlled crossover trial. Lancet 2002, 360:978–984.

    Article  PubMed  CAS  Google Scholar 

  24. Saiman L, Marshall BC, Mayer-Hamblett N, et al.: Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 2003, 290:1749–1756.

    Article  PubMed  CAS  Google Scholar 

  25. Clement A, Tamalet A, Le Roux E, et al.: Long term effects of azithromycin in patients with cystic fibrosis: a double-blind, placebo-controlled trial. Thorax 2006, 61:895–902.

    Article  PubMed  CAS  Google Scholar 

  26. Altschuler EL: Azithromycin, the multi-drug resistance protein, and cystic fibrosis. Lancet 1998, 351:1286.

    Article  PubMed  CAS  Google Scholar 

  27. Szefler SJ, Brenner M, Jusko WJ, et al.: Dose-and time-related effects of troleandomycin on methylprednisolone elimination. Clin Pharmacol Ther 1982, 32:166–171.

    Article  PubMed  CAS  Google Scholar 

  28. Rubin BK: Immunomodulatory properties of macrolides: overview and historical perspective. Am J Med 2004, 117(Suppl 9A):2S–4S.

    PubMed  Google Scholar 

  29. Shoji T, Yoshida S, Sakamoto H, et al.: Anti-inflammatory effect of roxithromycin in patients with aspirin-intolerant asthma. Clin Exp Allergy 1999, 29:950–956.

    Article  PubMed  CAS  Google Scholar 

  30. Amayasu H, Yoshida S, Ebana S: Clarithromycin suppresses bronchial hyperresponsiveness associated with eosinophilic inflammation in patients with asthma. Ann Allergy Asthma Immunol 2000, 84:594–598.

    Article  PubMed  CAS  Google Scholar 

  31. Black PN, Blasi F, Jenkins CR, et al.: Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae. Am J Respir Crit Care Med 2001, 164:536–541.

    PubMed  CAS  Google Scholar 

  32. Kraft M, Cassell GH, Pak J, Martin RJ: Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Chest 2002, 121:1782–1788.

    Article  PubMed  CAS  Google Scholar 

  33. Majima Y: Clinical implications of the immunomodulatory effects of macrolides on sinusitis. Am J Med 2004, 117(Suppl 9A):20S–25S.

    PubMed  CAS  Google Scholar 

  34. Gotfried MH: Macrolides for the treatment of chronic sinusitis, asthma, and COPD. Chest 2004, 125(Suppl 2):52S–16S.

    Article  PubMed  CAS  Google Scholar 

  35. Rubin BK, Henke MO: Immunomodulatory activity and effectiveness of macrolides in chronic airway disease. Chest 2004, 125(Suppl 2):70S–78S.

    Article  PubMed  CAS  Google Scholar 

  36. Kadota J, Mukae H, Ishii H, et al.: Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis. Respir Med 2003, 97:844–850.

    Article  PubMed  CAS  Google Scholar 

  37. Bell SC, Senini SL, McCormack JG: Macrolides in cystic fibrosis. Chron Respir Dis 2005, 2:85–98.

    Article  PubMed  CAS  Google Scholar 

  38. Fecik RA, Nguyen PL, Venkatraman L: Approaches to the synthesis of immunolides: selective immunomodulatory macroides for cystic fibrosis. Curr Opin Drug Discov Devel 2005, 8:741–747.

    PubMed  CAS  Google Scholar 

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Correspondence to Daniel P. Healy PharmD.

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Healy, D.P. Macrolide immunomodulation of chronic respiratory diseases. Curr Infect Dis Rep 9, 7–13 (2007). https://doi.org/10.1007/s11908-007-0016-1

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