Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Respiratory Research
Published in: Respiratory Research 1/2010

Open Access 01-12-2010 | Research

Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis

Authors: Avraham Beigelman, Cassandra L Mikols, Sean P Gunsten, Carolyn L Cannon, Steven L Brody, Michael J Walter

Published in: Respiratory Research | Issue 1/2010

Login to get access

Abstract

Background

Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation.

Methods

Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV), and treated daily with PBS or azithromycin for 7 days post-inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL).

Results

Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8), azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21.

Conclusions

In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences.
Literature
1.
Glezen WP, Taber LH, Frank AL, Kasel JA: Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 1986,140(6):543–546.PubMed
2.
Boyce TG, Mellen BG, Mitchel EF Jr, Wright PF, Griffin MR: Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr 2000,137(6):865–870.CrossRefPubMed
3.
Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ: Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA 1999,282(15):1440–1446.CrossRefPubMed
4.
Leader S, Kohlhase K: Respiratory syncytial virus-coded pediatric hospitalizations, 1997 to 1999. Pediatr Infect Dis J 2002,21(7):629–632.CrossRefPubMed
5.
Sigurs N: Epidemiologic and clinical evidence of a respiratory syncytial virus-reactive airway disease link. Am J Respir Crit Care Med 2001,163(3 Pt 2):S2–6.CrossRefPubMed
6.
Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B: Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000,161(5):1501–1507.CrossRefPubMed
7.
Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, Kjellman B: Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med 2005,171(2):137–141.CrossRefPubMed
8.
Castro M, Schweiger T, Yin-Declue H, Ramkumar TP, Christie C, Zheng J, Cohen R, Schechtman KB, Strunk R, Bacharier LB: Cytokine response after severe respiratory syncytial virus bronchiolitis in early life. J Allergy Clin Immunol 2008,122(4):726–733.CrossRefPubMedPubMedCentral
9.
Carroll KN, Wu P, Gebretsadik T, Griffin MR, Dupont WD, Mitchel EF, Hartert TV: The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma. J Allergy Clin Immunol 2009,123(5):1055–1061.CrossRefPubMedPubMedCentral
10.
Glezen WP, Greenberg SB, Atmar RL, Piedra PA, Couch RB: Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA 2000,283(4):499–505.CrossRefPubMed
11.
Diagnosis and management of bronchiolitis Pediatrics 2006,118(4):1774–1793.
12.
Shinkai M, Rubin BK: Macrolides and airway inflammation in children. Paediatr Respir Rev 2005,6(3):227–235.CrossRefPubMed
13.
14.
Equi A, Balfour-Lynn IM, Bush A, Rosenthal M: Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial. Lancet 2002,360(9338):978–984.CrossRefPubMed
15.
Miyatake H, Taki F, Taniguchi H, Suzuki R, Takagi K, Satake T: Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma. Chest 1991,99(3):670–673.CrossRefPubMed
16.
Shimizu T, Kato M, Mochizuki H, Tokuyama K, Morikawa A, Kuroume T: Roxithromycin reduces the degree of bronchial hyperresponsiveness in children with asthma. Chest 1994,106(2):458–461.CrossRefPubMed
17.
Kamoi H, Kurihara N, Fujiwara H, Hirata K, Takeda T: The macrolide antibacterial roxithromycin reduces bronchial hyperresponsiveness and superoxide anion production by polymorphonuclear leukocytes in patients with asthma. J Asthma 1995,32(3):191–197.CrossRefPubMed
18.
Shimizu T, Kato M, Mochizuki H, Takei K, Maeda S, Tokuyama K, Morikawa A: Roxithromycin attenuates acid-induced cough and water-induced bronchoconstriction in children with asthma. J Asthma 1997,34(3):211–217.CrossRefPubMed
19.
Amayasu H, Yoshida S, Ebana S, Yamamoto Y, Nishikawa T, Shoji T, Nakagawa H, Hasegawa H, Nakabayashi M, Ishizaki Y: Clarithromycin suppresses bronchial hyperresponsiveness associated with eosinophilic inflammation in patients with asthma. Ann Allergy Asthma Immunol 2000,84(6):594–598.CrossRefPubMed
20.
Black PN, Blasi F, Jenkins CR, Scicchitano R, Mills GD, Rubinfeld AR, Ruffin RE, Mullins PR, Dangain J, Cooper BC, David DB, Allegra L: Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae. Am J Respir Crit Care Med 2001,164(4):536–541.CrossRefPubMed
21.
Ekici A, Ekici M, Erdemoglu AK: Effect of azithromycin on the severity of bronchial hyperresponsiveness in patients with mild asthma. J Asthma 2002,39(2):181–185.CrossRefPubMed
22.
Kraft M, Cassell GH, Pak J, Martin RJ: Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Chest 2002,121(6):1782–1788.CrossRefPubMed
23.
Kostadima E, Tsiodras S, Alexopoulos EI, Kaditis AG, Mavrou I, Georgatou N, Papamichalopoulos A: Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma. Eur Respir J 2004,23(5):714–717.CrossRefPubMed
24.
Johnston SL, Blasi F, Black PN, Martin RJ, Farrell DJ, Nieman RB: The effect of telithromycin in acute exacerbations of asthma. N Engl J Med 2006,354(15):1589–1600.CrossRefPubMed
25.
Piacentini GL, Peroni DG, Bodini A, Pigozzi R, Costella S, Loiacono A, Boner AL: Azithromycin reduces bronchial hyperresponsiveness and neutrophilic airway inflammation in asthmatic children: a preliminary report. Allergy Asthma Proc 2007,28(2):194–198.CrossRefPubMed
26.
Kneyber MC, van Woensel JB, Uijtendaal E, Uiterwaal CS, Kimpen JL: Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease: a randomized equivalence trial. Pediatr Pulmonol 2008,43(2):142–149.CrossRefPubMed
27.
Tahan F, Ozcan A, Koc N: Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial. Eur Respir J 2007,29(1):91–97.CrossRefPubMed
28.
Kim EY, Battaile JT, Patel AC, You Y, Agapov E, Grayson MH, Benoit LA, Byers DE, Alevy Y, Tucker J, Swanson S, Tidwell R, Tyner JW, Morton JD, Castro M, Polineni D, Patterson GA, Schwendener RA, Allard JD, Peltz G, Holtzman MJ: Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med 2008,14(6):633–640.CrossRefPubMedPubMedCentral
29.
Walter MJ, Morton JD, Kajiwara N, Agapov E, Holtzman MJ: Viral induction of a chronic asthma phenotype and genetic segregation from the acute response. J Clin Invest 2002,110(2):165–175.CrossRefPubMedPubMedCentral
30.
Beigelman A, Gunsten S, Mikols CL, Vidavsky I, Cannon CL, Brody SL, Walter MJ: Azithromycin Attenuates Airway Inflammation in a Noninfectious Mouse Model of Allergic Asthma. Chest 2009,136(2):498–506.CrossRefPubMed
31.
Gunsten S, Mikols CL, Grayson MH, Schwendener RA, Agapov E, Tidwell RM, Cannon CL, Brody SL, Walter MJ: IL-12 p80-dependent macrophage recruitment primes the host for increased survival following a lethal respiratory viral infection. Immunology 2009,126(4):500–513.CrossRefPubMedPubMedCentral
32.
Mikols CL, Yan L, Norris JY, Russell TD, Khalifah AP, Hachem RR, Chakinala MM, Yusen RD, Castro M, Kuo E, Patterson GA, Mohanakumar T, Trulock EP, Walter MJ: IL-12 p80 is an innate epithelial cell effector that mediates chronic allograft dysfunction. Am J Respir Crit Care Med 2006,174(4):461–470.CrossRefPubMedPubMedCentral
33.
Russell TD, Yan Q, Fan G, Khalifah AP, Bishop DK, Brody SL, Walter MJ: IL-12 p40 homodimer-dependent macrophage chemotaxis and respiratory viral inflammation are mediated through IL-12 receptor beta 1. J Immunol 2003,171(12):6866–6874.CrossRefPubMed
34.
Hoffmann N, Lee B, Hentzer M, Rasmussen TB, Song Z, Johansen HK, Givskov M, Hoiby N: Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary-growth-phase killing of Pseudomonas aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr(-/-) mice. Antimicrob Agents Chemother 2007,51(10):3677–3687.CrossRefPubMedPubMedCentral
35.
Conte JE Jr, Golden J, Duncan S, McKenna E, Lin E, Zurlinden E: Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects. Antimicrob Agents Chemother 1996,40(7):1617–1622.PubMedPubMedCentral
36.
Bao Z, Lim S, Liao W, Lin Y, Thiemermann C, Leung BP, Wong WS: Glycogen synthase kinase-3beta inhibition attenuates asthma in mice. Am J Respir Crit Care Med 2007,176(5):431–438.CrossRefPubMed
37.
Duan W, Chan JH, Wong CH, Leung BP, Wong WS: Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. J Immunol 2004,172(11):7053–7059.CrossRefPubMed
38.
Look DC, Walter MJ, Williamson MR, Pang L, You Y, Sreshta JN, Johnson JE, Zander DS, Brody SL: Effects of paramyxoviral infection on airway epithelial cell Foxj1 expression, ciliogenesis, and mucociliary function. Am J Pathol 2001,159(6):2055–2069.CrossRefPubMedPubMedCentral
39.
Sato K, Suga M, Akaike T, Fujii S, Muranaka H, Doi T, Maeda H, Ando M: Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice. Am J Respir Crit Care Med 1998,157(3 Pt 1):853–857.CrossRefPubMed
40.
Asada M, Yoshida M, Suzuki T, Hatachi Y, Sasaki T, Yasuda H, Nakayama K, Nishimura H, Nagatomi R, Kubo H, Yamaya M: Macrolide antibiotics inhibit respiratory syncytial virus infection in human airway epithelial cells. Antiviral Res 2009,83(2):191–200.CrossRefPubMed
41.
Ivetic Tkalcevic V, Bosnjak B, Hrvacic B, Bosnar M, Marjanovic N, Ferencic Z, Situm K, Culic O, Parnham MJ, Erakovic V: Anti-inflammatory activity of azithromycin attenuates the effects of lipopolysaccharide administration in mice. Eur J Pharmacol 2006,539(1–2):131–138.CrossRefPubMed
42.
Leiva M, Ruiz-Bravo A, Jimenez-Valera M: Effects of telithromycin in in vitro and in vivo models of lipopolysaccharide-induced airway inflammation. Chest 2008,134(1):20–29.CrossRefPubMed
43.
Tsai WC, Rodriguez ML, Young KS, Deng JC, Thannickal VJ, Tateda K, Hershenson MB, Standiford TJ: Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection. Am J Respir Crit Care Med 2004,170(12):1331–1339.CrossRefPubMed
44.
Harcourt JL, Karron RA, Tripp RA: Anti-G protein antibody responses to respiratory syncytial virus infection or vaccination are associated with inhibition of G protein CX3C-CX3CR1 binding and leukocyte chemotaxis. J Infect Dis 2004,190(11):1936–1940.CrossRefPubMed
45.
Zhang W, Choi Y, Haynes LM, Harcourt JL, Anderson LJ, Jones LP, Tripp RA: Vaccination to induce antibodies blocking the CX3C-CX3CR1 interaction of respiratory syncytial virus G protein reduces pulmonary inflammation and virus replication in mice. J Virol 84(2):1148–1157.
46.
Haynes LM, Caidi H, Radu GU, Miao C, Harcourt JL, Tripp RA, Anderson LJ: Therapeutic monoclonal antibody treatment targeting respiratory syncytial virus (RSV) G protein mediates viral clearance and reduces the pathogenesis of RSV infection in BALB/c mice. J Infect Dis 2009,200(3):439–447.CrossRefPubMed
47.
Kawasaki S, Takizawa H, Ohtoshi T, Takeuchi N, Kohyama T, Nakamura H, Kasama T, Kobayashi K, Nakahara K, Morita Y, Yamamoto K: Roxithromycin inhibits cytokine production by and neutrophil attachment to human bronchial epithelial cells in vitro. Antimicrob Agents Chemother 1998,42(6):1499–1502.PubMedPubMedCentral
48.
Adachi T, Motojima S, Hirata A, Fukuda T, Kihara N, Kosaku A, Ohtake H, Makino S: Eosinophil apoptosis caused by theophylline, glucocorticoids, and macrolides after stimulation with IL-5. J Allergy Clin Immunol 1996,98(6 Pt 2):S207–215.CrossRefPubMed
49.
50.
Metadata
Title
Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
Authors
Avraham Beigelman
Cassandra L Mikols
Sean P Gunsten
Carolyn L Cannon
Steven L Brody
Michael J Walter
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-11-90

Other articles of this Issue 1/2010

Respiratory Research 1/2010 Go to the issue

Research

Allergen particle binding by human primary bronchial epithelial cells is modulated by surfactant protein D

Research

Intracerebroventricular injection of leukotriene B4 attenuates antigen-induced asthmatic response via BLT1 receptor stimulating HPA-axis in sensitized rats

Research

Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function

Review

The role of leptin in the respiratory system: an overview

Research

Cytotoxic T cells expressing the co-stimulatory receptor NKG2 D are increased in cigarette smoking and COPD

Research

Long acting β2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits