Gefitinib decreased lung fibrosis, but worsened inflammation, in rats

The early study suggested that TGF-α overexpression caused pulmonary fibrosis in transgenic mice [ref1], whereas TGF-α deficiency reduced pulmonary fibrosis in TGF-α knockout mice [ref2]. Therefore, it is plausible to treat patients with IPF by inhibition of TGF-α/EGF signaling. In a bleomycin-induced lung fibrosis model in mice,  it was shown that EGFR tyrosine kinase inhibitors, gefitinib and AG1478. Both inhibitors attenuated lung fibrosis [ref3].

Recently, Dr. Sone group examined the effect of gefitinib in a radiation induced injury model in rats. The new study found that gefitinib attenuated fibrotic lung remodeling, but exaggerated lung inflammation [ref4].



References

Hardie WD, Le Cras TD, Jiang K, Tichelaar JW, Azhar M, Korfhagen TR. Conditional expression of transforming growth factor-alpha in adult mouse lung causes pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2004;286:L741–L749.


Madtes DK, Elston AL, Hackman RC, Dunn AR, Clark JG. Transforming growth factor-alpha deficiency reduces pulmonary fibrosis in transgenic mice. Am J Respir Cell Mol Biol 1999;20:924–934.

Ishii Y, Fujimoto S, Fukuda T. Gefitinib prevents bleomycin-induced lung
fibrosis in mice. Am J Respir Crit Care Med. 2006 Sep 1;174(5):550-6. Epub 2006
Jun 1. PubMed PMID: 16741154.

Miyake K, Tani K, Kakiuchi S, Suzuka C, Toyoda Y, Kishi J, Tezuka T, Yuasa S,
Hanibuchi M, Aono Y, Nishioka Y, Sone S. Epidermal growth factor
receptor-tyrosine kinase inhibitor (gefitinib) augments pneumonitis, but
attenuates lung fibrosis in response to radiation injury in rats. J Med Invest.
2012;59(1-2):174-85. PubMed PMID: 22450006.