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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

MacDonald, Brian A; Chakravarthy, Krishnan V; Davidson, Bruce A; Mullan, Barbara A; Alluri, Ravi; Hakansson, Anders P LU and Knight, Paul R (2015) In Anesthesiology 123(3). p.590-602
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... (More)

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.

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published
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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
in
Anesthesiology
volume
123
issue
3
pages
13 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:84946919500
ISSN
1528-1175
DOI
10.1097/ALN.0000000000000766
language
English
LU publication?
yes
id
3c2f74b4-a2f9-4215-85aa-4472fc814554
date added to LUP
2016-05-20 17:57:09
date last changed
2017-05-29 15:43:53
@article{3c2f74b4-a2f9-4215-85aa-4472fc814554,
  abstract     = {<p>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).</p><p>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.</p><p>RESULTS: Halothane exposure resulted in decreased bacterial burden (7.9 ± 3.9 × 10 vs. 3.4 ± 1.6 × 10 colony-forming units, P &lt; 0.01), clinical score (0.6 ± 0.2 vs. 2.3 ± 0.2, P &lt; 0.0001), and lung injury (as measured by bronchoalveolar lavage albumin, 1.5 ± 0.7 vs. 6.8 ± 1.6 mg/ml, P &lt; 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.</p><p>CONCLUSION: These findings indicate that the use of halogenated volatile anesthetics modulates the type I IFN response to influenza and enhance postinfection antibacterial immunity.</p>},
  author       = {MacDonald, Brian A and Chakravarthy, Krishnan V and Davidson, Bruce A and Mullan, Barbara A and Alluri, Ravi and Hakansson, Anders P and Knight, Paul R},
  issn         = {1528-1175},
  keyword      = {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},
  language     = {eng},
  number       = {3},
  pages        = {590--602},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Anesthesiology},
  title        = {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},
  url          = {http://dx.doi.org/10.1097/ALN.0000000000000766},
  volume       = {123},
  year         = {2015},
}