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Transient expression of IL-1 beta induces acute lung injury and chronic repair leading to pulmonary fibrosis

Transient expression of IL-1 beta induces acute lung injury and chronic repair leading to pulmonary fibrosis
Transient expression of IL-1 beta induces acute lung injury and chronic repair leading to pulmonary fibrosis
L-1? is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1? in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1? in rat lungs after intratracheal administration. The high expression of IL-1? in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-? and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-?1 were increased in lung fluid samples 1 week after peak expression of IL-1?. Although PDGF returned to baseline in the third week, TGF-?1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1?, converts to progressive fibrotic changes. IL-1? should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.
0021-9738
1529-1536
Kolb, Martin
f7169cba-735d-4c03-b348-55f170d1b5dd
Margetts, Peter J.
d7386682-aba2-4182-b742-94ea4c6262b6
Anthony, Daniel C.
928249fa-dcf4-4088-b95b-ce14c719164d
Pitossi, Fernando
b5e78a06-f2de-4ce9-b310-d116017a665d
Gauldie, Jack
7ec6f101-1eff-45d7-85be-ced183526ea2
Kolb, Martin
f7169cba-735d-4c03-b348-55f170d1b5dd
Margetts, Peter J.
d7386682-aba2-4182-b742-94ea4c6262b6
Anthony, Daniel C.
928249fa-dcf4-4088-b95b-ce14c719164d
Pitossi, Fernando
b5e78a06-f2de-4ce9-b310-d116017a665d
Gauldie, Jack
7ec6f101-1eff-45d7-85be-ced183526ea2

Kolb, Martin, Margetts, Peter J., Anthony, Daniel C., Pitossi, Fernando and Gauldie, Jack (2001) Transient expression of IL-1 beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. Journal of Clinical Investigation, 107 (12), 1529-1536. (doi:10.1172/JCI12568).

Record type: Article

Abstract

L-1? is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1? in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1? in rat lungs after intratracheal administration. The high expression of IL-1? in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-? and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-?1 were increased in lung fluid samples 1 week after peak expression of IL-1?. Although PDGF returned to baseline in the third week, TGF-?1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1?, converts to progressive fibrotic changes. IL-1? should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.

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More information

Submitted date: 20 February 2001
Published date: 15 June 2001

Identifiers

Local EPrints ID: 55565
URI: http://eprints.soton.ac.uk/id/eprint/55565
ISSN: 0021-9738
PURE UUID: 1e811dd6-c163-4ef8-b127-d1badb6dfb0f

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Date deposited: 01 Aug 2008
Last modified: 15 Mar 2024 10:56

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Contributors

Author: Martin Kolb
Author: Peter J. Margetts
Author: Daniel C. Anthony
Author: Fernando Pitossi
Author: Jack Gauldie

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