Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice.

Abstract

Antiviral immune responses play as a double edged sword in resolution of infection and pathogenesis of acute lung injury caused by infection with highly pathogenic influenza A viruses. Here we show that type I interferons (IFNs) are important in protection against acute influenza A virus infection not only via their antiviral activity but also via their anti-inflammatory activity. IFN α receptor (IFNAR) knock-out (KO) mice exhibited increased mortality and morbidity with higher viral load after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) compared with wild-type (WT) mice, though the viruses were finally eliminated in both groups. The levels of proinflammatory cytokines in the lungs were significantly higher, while the level of IL-10 in the lungs was significantly lower in IFNAR KO mice than in WT mice during the course of infection. Restoration of IL-10 during an ongoing virus infection significantly reduced the levels of proinflammatory cytokines and improved mortality of IFNAR KO mice. These results suggest that type I IFNs are responsible not only for direct resolution of viral load but also for suppression of immunopathology caused by influenza A virus through IL-10 production.

• Authors: Yojiro Arimori, Risa Nakamura, Hisakata Yamada, Kensuke Shibata, Naoyoshi Maeda, Tetsuo Kase, Yasunobu Yoshikai
• Journal: Antiviral research (Antiviral Res) Vol. 99 Issue 3 Pg. 230-7 (Sep 2013) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 23721943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Interferon Type I
• Interleukin-10
• Receptor, Interferon alpha-beta

Topics

• Acute Lung Injury (drug therapy, immunology, mortality, virology)
• Animals
• Antiviral Agents (administration & dosage)
• Down-Regulation (drug effects)
• Female
• Humans
• Influenza A Virus, H1N1 Subtype (drug effects, genetics, physiology)
• Influenza, Human (drug therapy, immunology, mortality, virology)
• Interferon Type I (administration & dosage)
• Interleukin-10 (genetics, immunology)
• Lung (drug effects, immunology, virology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptor, Interferon alpha-beta (deficiency, genetics)