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Respir Res. 2015 Sep 15;16:105. doi: 10.1186/s12931-015-0264-9.

Uridine supplementation exerts anti-inflammatory and anti-fibrotic effects in an animal model of pulmonary fibrosis.

Author information

1
Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
2
Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany. marco.idzko@uniklinik-freiburg.de.
3
Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany. tobmueller@ukaachen.de.
4
Department of Internal Medicine I, University Hospital RWTH Aachen, Aachen, Germany. tobmueller@ukaachen.de.

Abstract

RATIONALE:

Pulmonary fibrosis is a progressive disease with only few treatment options available at the moment. Recently, the nucleoside uridine has been shown to exert anti-inflammatory effects in different animal models, e.g. in acute lung injury or bronchial asthma.

METHOD:

Therefore, we investigated the influence of uridine supplementation on inflammation and fibrosis in the classical bleomycin model. Male C57BL/6 mice received an intratracheal injection of bleomycin on day 0 and were treated intraperitoneally with uridine or vehicle. The degree of inflammation and fibrosis was assessed at different time points.

RESULTS:

Uridine administration resulted in attenuated inflammation, as demonstrated by reduced leukocytes and pro-inflammatory cytokines in the broncho-alveolar lavage (BAL) fluid. Furthermore, collagen deposition in the lung interstitium was also reduced by uridine supplementation. Similar results were obtained in a model in which animals received repeated intraperitoneal bleomycin injections. In addition uridine inhibited collagen and TGF-ß synthesis by primary lung fibroblasts, the release of pro-inflammatory cytokines by human lung epithelial cells, as well as the production of reactive oxygen species by human neutrophils.

CONCLUSION:

In summary, we were able to show that uridine has potent anti-inflammatory and anti-fibrotic properties. As uridine supplementation has been shown to be well tolerated and safe in humans, this might be a new therapeutic approach for the treatment of fibrotic lung diseases.

PMID:
26369416
PMCID:
PMC4570657
DOI:
10.1186/s12931-015-0264-9
[Indexed for MEDLINE]
Free PMC Article

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