Repression of bleomycin-induced pneumopathy by TNF.
Idiopathic pulmonary fibrosis is a chronic inflammatory lung disease with interstitial fibrosis. As a potent proinflammatory cytokine, TNF has been suggested to play critical roles in the pathogenesis of the human disease and its animal model, bleomycin-induced pneumopathy. However, studies using TNF-deficient mice have demonstrated that TNF also has an anti-inflammatory function. To determine the role of TNF in pulmonary inflammation induced by bleomycin, we injected bleomycin intratracheally into TNF-deficient mice. In this study, we demonstrated persistent and intense inflammation in TNF-deficient mice due to reduced apoptosis of inflammatory cells. We also showed that in TNF-deficient mice, challenge via airways with murine, but not human rTNF, efficiently eliminated inflammatory cells from the bronchoalveolar space by apoptosis, and thus promoted tissue repair of damaged lungs. Contrary to previous reports that showed that TNF was a central mediator of pulmonary inflammation, we have demonstrated that TNF is essential for repressing pulmonary inflammation in bleomycin-induced pneumopathy.
Kuroki
Misuzu
M
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Noguchi
Yuji
Y
Shimono
Michihide
M
Tomono
Kazunori
K
Tashiro
Takayoshi
T
Obata
Yuichi
Y
Nakayama
Eiichi
E
Kohno
Shigeru
S
D000280:Administration, Inhalation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001761:Bleomycin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin