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. 2006 Oct;61(10):886-94.
doi: 10.1136/thx.2005.056317. Epub 2006 Jun 29.

In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-beta in the lung

K Nakagome  1 , M Dohi, K Okunishi, R Tanaka, J Miyazaki, K Yamamoto
Affiliations

In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-beta in the lung

K Nakagome et al. Thorax. 2006 Oct.

Abstract

Background: Idiopathic pulmonary fibrosis is a devastating disorder for which there is no effective treatment. Transforming growth factor (TGF)-beta plays a critical role in provoking fibrosis. Interleukin (IL)-10 is a potent immunosuppressive cytokine but its effect on the fibrosing process is unclear. A study was undertaken to examine whether IL-10 affects the production and activation of TGF-beta and thus can attenuate the fibrosis.

Methods: Mice were given an intratracheal injection of bleomycin. On day 1 or 14, IL-10 gene was delivered by rapid intravenous injection of Ringer's solution containing plasmid. Two weeks after the plasmid injection the mice were examined for fibrosis. The effect of IL-10 on TGF-beta production by alveolar macrophages was assessed.

Results: Even when delivered during the fibrosing phase, IL-10 gene significantly suppressed the pathological findings, hydroxyproline content, and production of both active and total forms of TGF-beta1 in the lung. Immunohistochemical analyses showed that alveolar macrophages were one of the major sources of TGF-beta1 and IL-10 diminished the intensity of the staining. IL-10 also suppressed the expression of alphaV beta6 integrin, a molecule that plays an important role in TGF-beta activation, on lung epithelial cells. Alveolar macrophages from bleomycin injected mice produced TGF-beta1 spontaneously ex vivo, which was significantly suppressed by treatment of the mice in vivo or by treatment of the explanted macrophages ex vivo with IL-10.

Conclusion: IL-10 suppresses the production and activation of TGF-beta in the lung and thus attenuates pulmonary fibrosis, even when delivered in the chronic phase.

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Conflict of interest statement

Competing interests: none.

Comment in

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