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Inflammation

, Volume 36, Issue 4, pp 812–820 | Cite as

Low-dose Interferon-α Treatment Improves Survival and Inflammatory Responses in a Mouse Model of Fulminant Acute Respiratory Distress Syndrome

  • Daisuke Kudo
  • Kazuko Uno
  • Tetsuji Aoyagi
  • Yukiko Akahori
  • Keiko Ishii
  • Emi Kanno
  • Ryoko Maruyama
  • Shigeki Kushimoto
  • Mitsuo Kaku
  • Kazuyoshi KawakamiEmail author
Article
  • 364 Downloads

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.

KEY WORDS

ARDS IFN-α anti-inflammatory effects IFN-γ NKT cells 

Notes

Acknowledgments

This study was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Challenging Exploratory Research (23659841)) and a grant from the Ministry of Health, Labor, and Welfare of Japan (Research on Emerging and Re-emerging Infectious Diseases; 22-SHINKOU-IPPAN-014).

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Daisuke Kudo
    • 1
    • 2
  • Kazuko Uno
    • 3
  • Tetsuji Aoyagi
    • 4
  • Yukiko Akahori
    • 1
  • Keiko Ishii
    • 1
  • Emi Kanno
    • 5
  • Ryoko Maruyama
    • 5
  • Shigeki Kushimoto
    • 2
  • Mitsuo Kaku
    • 4
  • Kazuyoshi Kawakami
    • 1
    Email author
  1. 1.Department of Medical Microbiology, Mycology and ImmunologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of Emergency MedicineTohoku University Graduate School of MedicineSendaiJapan
  3. 3.Louis Pasteur Center for Medical ResearchKyotoJapan
  4. 4.Department of Infection Control and Laboratory Diagnostics, Internal MedicineTohoku University Graduate School of MedicineSendaiJapan
  5. 5.Department of Science of Nursing PracticeTohoku University Graduate School of MedicineSendaiJapan

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