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The macrolide clarithromycin inhibits experimental post-transplant bronchiolitis obliterans.

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.
AuthorsK Remund, T Rechsteiner, Z Guo, K Rentsch, A Boehler
JournalExperimental lung research (Exp Lung Res) Vol. 35 Issue 10 Pg. 830-40 (Dec 2009) ISSN: 1521-0499 [Electronic] England
PMID19995277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Clarithromycin
Topics
  • Animals
  • Anti-Bacterial Agents (pharmacology)
  • Bronchiolitis Obliterans (etiology, genetics, pathology, prevention & control)
  • Clarithromycin (pharmacology)
  • Graft Rejection (genetics, prevention & control)
  • Humans
  • Immunosuppressive Agents (pharmacology)
  • Lung Transplantation (adverse effects)
  • Male
  • Matrix Metalloproteinase 2 (genetics)
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Trachea (metabolism, pathology, transplantation)
  • Transplantation, Heterotopic
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha (genetics)

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