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.
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.
  
  
  CONCLUSIONS
  These findings indicate that the use of halogenated volatile anesthetics modulates the type I IFN response to influenza and enhance postinfection antibacterial immunity.
authors.affiliation: From the Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, New York (B.A. MacDonald, A.P.H., P.R.K.); Department of Anesthesiology, Veterans Administration Western New York Healthcare System, Buffalo, New York (B.A. MacDonald, B.A.D., B.A. Mullan, R.A., P.R.K.); Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland (K.V.C.); and Department of Anesthesiology, State University of New York at Buffalo, Buffalo, New York (B.A.D., B.A. Mullan, R.A., P.R.K.).
authors.forename: Brian A
authors.initials: BA
authors.lastname: MacDonald
authors.forename: Krishnan V
authors.initials: KV
authors.lastname: Chakravarthy
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Mullan
authors.forename: Ravi
authors.initials: R
authors.lastname: Alluri
authors.forename: Anders P
authors.initials: AP
authors.lastname: Hakansson
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006221:Halothane / Q000008:administration & dosage*; D053118:Influenza A Virus, H1N1 Subtype; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000188:drug therapy*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000209:etiology; D013296:Streptococcus pneumoniae
chemical_list: D018685:Anesthetics, Inhalation; D007370:Interferon Type I; D006221:Halothane