Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis
J Nagano, K Iyonaga, K Kawamura… - European …, 2006 - Eur Respiratory Soc
J Nagano, K Iyonaga, K Kawamura, A Yamashita, H Ichiyasu, T Okamoto, M Suga, Y Sasaki…
European Respiratory Journal, 2006•Eur Respiratory SocIdiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The
immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-β-
induced collagen deposition in vitro, and is widely used in Japan as a potent antifibrotic
agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in
the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the
antifibrotic effect of FK506. The inhibitory effect of FK506 on collagen synthesis in cultured …
immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-β-
induced collagen deposition in vitro, and is widely used in Japan as a potent antifibrotic
agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in
the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the
antifibrotic effect of FK506. The inhibitory effect of FK506 on collagen synthesis in cultured …
Idiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-β-induced collagen deposition in vitro, and is widely used in Japan as a potent antifibrotic agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the antifibrotic effect of FK506.
The inhibitory effect of FK506 on collagen synthesis in cultured lung fibroblastic cells, TIG-3-20, and its antifibrotic effect on bleomycin (BLM)-induced pulmonary fibrosis in mice was investigated.
FK506 inhibited TGF-β-induced collagen synthesis, and suppressed the expression of TGF-β type I receptor (TβR-I) in TIG-3-20 cells. Consistent with the in vitro findings, FK506 treatment starting on day 6 attenuated BLM-induced pulmonary fibrosis, in part, via reduced TβR-I expression. FK506 treatment in the acute BLM injury phase unexpectedly increased pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and enhanced lung injury, resulting in poor survival.
In conclusion, the present results suggest that FK506 has a potent antifibrotic effect and may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury.
European Respiratory Society