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The macrolide clarithromycin inhibits experimental posttransplant bronchiolitis obliterans


Remund, K; Rechsteiner, T; Guo, Z; Rentsch, K; Boehler, A (2009). The macrolide clarithromycin inhibits experimental posttransplant bronchiolitis obliterans. Experimental Lung Research, 35(10):830-840.

Abstract

Chronic allograft dysfunction in form of bronchiolitis obliterans is the most important hurdle to improved longterm survival after clinical lung transplantation to date. Recently, it was observed that the progression of bronchiolitis obliterans in lung transplant recipients might be inhibited by macrolide antibiotics. The authors therefore tested whether macrolide therapy can attenuate fibrous obliteration of airways in an animal model of bronchiolitis obliterans. Rats with heterotopic tracheal allografts were treated intraperitoneally with clarithromycin and compared to untreated transplanted animals with respect to allograft histology and expression of selected cytokines. At day 21 after transplantation, the tracheal allografts of treated animals were free of fibrous material or partially occluded dependent of clarithromycin dosage. Untreated animals had completely obliterated allografts. In treated animals, tumor necrosis factor alpha (TNF-alpha) was down-regulated early (5 days) and late (21 days) post transplant, whereas interferon gamma (IFN-gamma) expression was decreased only early after transplantation. Transforming growth factor beta (TGF-beta) expression was not affected. Therapy with low-dose macrolides in post-transplant obliterative bronchiolitis is based on their immunomodulatory rather than antimicrobial properties. In the setting of lung transplantation, macrolides primarily act as modulators of the early inflammatory response to stressed, damaged, or infected cells.

Abstract

Chronic allograft dysfunction in form of bronchiolitis obliterans is the most important hurdle to improved longterm survival after clinical lung transplantation to date. Recently, it was observed that the progression of bronchiolitis obliterans in lung transplant recipients might be inhibited by macrolide antibiotics. The authors therefore tested whether macrolide therapy can attenuate fibrous obliteration of airways in an animal model of bronchiolitis obliterans. Rats with heterotopic tracheal allografts were treated intraperitoneally with clarithromycin and compared to untreated transplanted animals with respect to allograft histology and expression of selected cytokines. At day 21 after transplantation, the tracheal allografts of treated animals were free of fibrous material or partially occluded dependent of clarithromycin dosage. Untreated animals had completely obliterated allografts. In treated animals, tumor necrosis factor alpha (TNF-alpha) was down-regulated early (5 days) and late (21 days) post transplant, whereas interferon gamma (IFN-gamma) expression was decreased only early after transplantation. Transforming growth factor beta (TGF-beta) expression was not affected. Therapy with low-dose macrolides in post-transplant obliterative bronchiolitis is based on their immunomodulatory rather than antimicrobial properties. In the setting of lung transplantation, macrolides primarily act as modulators of the early inflammatory response to stressed, damaged, or infected cells.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:10 Mar 2010 09:32
Last Modified:05 Apr 2016 13:57
Publisher:Informa Healthcare
ISSN:0190-2148
Publisher DOI:https://doi.org/10.3109/01902140902918755
PubMed ID:19995277

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