Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF‐β and IL-10

Abstract

Modulation of cytokine expression represents a potentially useful approach for the treatment of idiopathic pulmonary fibrosis (IPF).To identify potential targets for such intervention, semi-quantitative reverse transcriptasepolymerase chain reaction was used to compare the expression of messenger ribonucleic acids (mRNAs) coding for 17 cytokines in lung tissue obtained from patients with IPF at the time of diagnosis and control subjects. Some cytokines were also studied at the protein level by immunohistochemical techniques.mRNAs coding for all of the cytokines evaluated were detected in both control and fibrotic lung samples. Only transforming growth factor (TGF)-b and interleukin (IL)-10 mRNAs were quantitatively increased in lung biopsies from patients with IPF compared with those of controls, results confirmed at the protein level by immunohistochemistry. Although mRNAs for platelet-derived growth factor (PDGF)-BB and keratinocyte growth factor (KGF) were expressed in similar amounts in lungs from patients with IPF and controls, localised accumulation of both factors was also observed in IPF. Hyperplastic alveolar epithelial cells were a prominent source of cytokines, where IL-10, PDGF-BB and KGF were present in increased amounts, although increased accumulation in fibroblasts, smooth-muscle cells and matrix components was also observed (PDGF-BB, TGF-b).These results offer new insights into the cytokines produced in the lung in idiopathic pulmonary fibrosis and suggest that modulation of the production of transforming growth factor-b and interleukin-10 may represent a potentially useful therapeutic strategy for this disabling disease.

Contribution of the Prostaglandin E2/E-Prostanoid 2 Receptor Signaling Pathway in Abscess Formation in Rat Zymosan-Induced Pleurisy

“…The predominant role of IL-10 is to reduce inflammation. However, increased expression of IL-10 significantly contributes to fibrosis (Bergeron et al, 2003;Barbarin et al, 2005). The present study also showed that treatment with NS-398 significantly decreased mRNA levels of TGF-␤1 and CTGF, which was again reversed by the EP 2 receptor agonist.…”

Cellular FLICE-like Inhibitory Protein Deviates Myofibroblast Fas-Induced Apoptosis Toward Proliferation during Lung Fibrosis

“…60) and subsequent fibrosis (61)(62)(63). On the other hand, Th1 cytokines such as TNF-a, IFN-g, and IL-2, which are known to act antifibrotically (61,64,65), were reported to annul resistance to Fas-induced apoptosis by a mechanism involving c-FLIP downregulation (66,67).…”

Transforming Growth Factor-β: Master Regulator of the Respiratory System in Health and Disease

“…TGF-b is fundamental to the pathogenesis of pulmonary fibrosis (Figure 2A) (50,(53)(54)(55)(56). In the lung, TGF-b is expressed by multiple cell types, including epithelial cells, macrophages, and fibroblasts, and levels are elevated in animal models and in patients with IPF (57)(58)(59)(60). Pulmonary expression of TGF-b is sufficient to induce progressive fibrosis in rodents (61); conversely, blocking TGF-b signaling inhibits fibrosis in rodent models (62,63).…”