Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo.
Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day -3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-beta-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.
Arai
T
T
Department of Molecular Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan. arai@imed3.med.osaka-u.ac.jp
Abe
K
K
Matsuoka
H
H
Yoshida
M
M
Mori
M
M
Goya
S
S
Kida
H
H
Nishino
K
K
Osaki
T
T
Tachibana
I
I
Kaneda
Y
Y
Hayashi
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D018014:Gene Transfer Techniques; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis; D018108:Respirovirus / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D016753:Interleukin-10; D003094:Collagen