FTS reduces bleomycin-induced cytokine and chemokine production and inhibits pulmonary fibrosis in mice.
Bleomycin (BLM), an antitumour drug, is known to cause interstitial pneumonia followed by pulmonary fibrosis, and has often been used to produce an animal model of pulmonary fibrosis. In the present study, we examined the effect of a nonapeptide thymic hormone, facteur thymique serique (FTS), on the murine lung fibrosis induced by intratracheal instillation of BLM. Treatment with FTS ameliorated BLM-induced fibrotic changes in a dose-dependent manner, as indicated by the reduced accumulation of hydroxyproline (HP). In addition, FTS suppressed BLM-induced cellular inflammatory response in the lungs, as evidenced by inhibition of increased lung weight, reduced accumulation of inflammatory leucocytes, including lymphocytes and neutrophils, but not macrophages, and less pronounced histopathological changes. Finally, BLM challenge increased the local synthesis of proinflammatory cytokines, TNF-alpha and IL-1beta and chemokines, MCP-1, MIP-1alpha RANTES, MIP-2 and KC, while administration of FTS suppressed the production of these cytokines, except for MCP-1. These effects of FTS were observed only when mice received intratracheal instillation with BLM. Considered collectively, our results indicated that FTS treatment ameliorated the cellular inflammatory responses and fibrotic changes in the lungs caused by BLM and such inhibition was well correlated with reduced synthesis of several fibrosis-related cytokines, and suggested that FTS may be potentially useful for the treatment of pulmonary fibrosis.
Yara
S
S
The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa and Mitsui Pharmaceuticals Inc., Chiba, Japan.
Kawakami
K
K
Kudeken
N
N
Tohyama
M
M
Teruya
K
K
Chinen
T
T
Awaya
A
A
Saito
A
A
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004353:Drug Evaluation, Preclinical; D005260:Female; D007249:Inflammation; D007322:Instillation, Drug; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D016676:Macrophages, Alveolar / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D020556:Neutrophil Infiltration; D009929:Organ Size / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013935:Thymic Factor, Circulating / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014132:Trachea
D018925:Chemokines; D016207:Cytokines; D001761:Bleomycin; D013935:Thymic Factor, Circulating