title: Low-dose interferon-α treatment improves survival and inflammatory responses in a mouse model of fulminant acute respiratory distress syndrome.
abstract: Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of symptoms, therapeutic strategies for this pathologic condition are still poorly developed. Interferon (IFN)-α is well known as an antiviral cytokine and low-dose IFN-α has been reported to show antiinflammatory effects. Therefore, we investigated how this cytokine affected ARDS in a mouse model. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of fulminant ARDS. These mice were then treated intranasally with IFN-α and their survival, lung weight, pathological findings, and cytokine production were evaluated. Administration of low-dose IFN-α prolonged survival of fulminant ARDS mice, but higher doses of IFN-α did not. Histological analysis showed that low-dose IFN-α treatment improved findings of diffuse alveolar damage in fulminant ARDS mice, which was associated with reduction in the wet/dry (W/D) lung weight ratio. Furthermore, IFN-γ production in the lungs was significantly reduced in IFN-α-treated mice, compared with control mice, but tumor necrosis factor (TNF)-α production was almost equivalent for both groups. Low-dose IFN-α shows antiinflammatory and therapeutic effects in a mouse model of fulminant ARDS, and reduced production of IFN-γ in the lung may be involved in the beneficial effect of this treatment.
authors: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors: Daisuke
authors: D
authors: Kudo
authors: Kazuko
authors: K
authors: Uno
authors: Tetsuji
authors: T
authors: Aoyagi
authors: Yukiko
authors: Y
authors: Akahori
authors: Keiko
authors: K
authors: Ishii
authors: Emi
authors: E
authors: Kanno
authors: Ryoko
authors: R
authors: Maruyama
authors: Shigeki
authors: S
authors: Kushimoto
authors: Mitsuo
authors: M
authors: Kaku
authors: Kazuyoshi
authors: K
authors: Kawakami
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005699:Galactosylceramides; D016898:Interferon-alpha / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005699:Galactosylceramides; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C493154:alpha-galactosylceramide; D007371:Interferon-gamma