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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Re-evaluation of Fibrogenic Cytokines in Lung Fibrosis

Author(s): Margaret Kelly, Martin Kolb, Phillipe Bonniaud and Jack Gauldie

Volume 9, Issue 1, 2003

Page: [39 - 49] Pages: 11

DOI: 10.2174/1381612033392341

Price: $65


Idiopathic Pulmonary Fibrosis (IPF) is a chronic interstitial lung disease which results in end-stage fibrosis. The pathogenesis is believed to be related to a dysregulation in cross-talk between inflammatory and structural cells, mediated by various cytokines, chemokines and growth factors, which are responsible for the maintenance of tissue homeostasis and which coordinate the response to injury. The large number of mediators involved and the complexity of their interaction makes it difficult to identify the factors responsible for initiation of fibrogenesis and progression to chronicity. Whether a mediator ’ s presence in fibrotic lung is as a result of tissue injury or if it playsan active role in disease onset and progression has been partly answered by the use of transient and / or permanent transgenic and gene knock-out approaches to over-express single factors at a time. Chemokines such as interleukin-8 (IL-8), RANTES, IP-10, MIG or lymphotactin, do not appear to induce fibrosis when over-expressed in rodent lung. Amongst many tested, four cytokines and growth factors have been found to be pro-fibrotic; IL-1β, which demonstrates marked inflammation, tissue damage and chronic fibrosis, TNF-?, which induces inflammation and mild fibrosis, and GM-CSF, which induces moderate inflammation and fibrosis. A common finding with these cytokines are increased lung TGF-β levels, proportionate to the degree of fibrosis generated, while TGF-β itself causes minor inflammation but marked progressive chronic fibrosis. A growth factor ‘downstream’ from the pro-fibrotic effects of TGF-β, CTGF, is a likely critical mediator. However, over-expression of CTGF produces only mild and reversible fibrosis.

Keywords: Fibrogenic Cytokines, cytokines, RANTES, lymphotactin, homeostasis

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