Halothane modulates the type i interferon response to influenza and minimizes the risk of secondary bacterial pneumonia through maintenance of neutrophil recruitment in an animal model

Brian A MacDonald, Krishnan V Chakravarthy, Bruce A Davidson, Barbara A Mullan, Ravi Alluri, Anders P Hakansson, Paul R Knight

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: To minimize the risk of pneumonia, many anesthesiologists delay anesthesia-requiring procedures when patients exhibit signs of viral upper respiratory tract infection. Postinfluenza secondary bacterial pneumonias (SBPs) are a major cause of morbidity and mortality. An increased host susceptibility to SBP postinfluenza has been attributed to physical damage to the pulmonary epithelium, but flu-induced effects on the immune system are being shown to also play an important role. The authors demonstrate that halothane mitigates the risk of SBP postflu through modulation of the effects of type I interferon (IFN).

METHODS: Mice (n = 6 to 15) were exposed to halothane or ketamine and treated with influenza and Streptococcus pneumoniae. Bronchoalveolar lavage and lung homogenate were procured for the measurement of inflammatory cells, cytokines, chemokines, albumin, myeloperoxidase, and bacterial load.

RESULTS: Halothane exposure resulted in decreased bacterial burden (7.9 ± 3.9 × 10 vs. 3.4 ± 1.6 × 10 colony-forming units, P < 0.01), clinical score (0.6 ± 0.2 vs. 2.3 ± 0.2, P < 0.0001), and lung injury (as measured by bronchoalveolar lavage albumin, 1.5 ± 0.7 vs. 6.8 ± 1.6 mg/ml, P < 0.01) in CD-1 mice infected with flu for 7 days and challenged with S. pneumoniae on day 6 postflu. IFN receptor A1 knockout mice similarly infected with flu and S. pneumoniae, but not exposed to halothane, demonstrated a reduction of lung bacterial burden equivalent to that achieved in halothane-exposed wild-type mice.

CONCLUSION: These findings indicate that the use of halogenated volatile anesthetics modulates the type I IFN response to influenza and enhance postinfection antibacterial immunity.

Original languageEnglish
Pages (from-to)590-602
Number of pages13
JournalAnesthesiology
Volume123
Issue number3
DOIs
Publication statusPublished - 2015 Sept

Subject classification (UKÄ)

  • Anesthesiology and Intensive Care
  • Infectious Medicine

Free keywords

  • Anesthetics, Inhalation
  • Animals
  • Disease Models, Animal
  • Dogs
  • Halothane
  • Influenza A Virus, H1N1 Subtype
  • Interferon Type I
  • Madin Darby Canine Kidney Cells
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration
  • Orthomyxoviridae Infections
  • Pneumonia, Bacterial
  • Streptococcus pneumoniae

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