title: Inhalation anesthetic-induced neuroinvasion by an attenuated strain of West Nile virus in mice.
abstract: There are contradictory reports regarding the effects of inhalation anesthetics on the immune system. Measurable immune responses have been studied in vitro, but little is known about the in vivo effects in the intact organism. We used an attenuated, non-neuroinvasive, nonlethal strain of the encephalitic West Nile virus, termed WN-25, which can become lethal in combination with environmental stressors, to study possible modulatory immune effects of inhalation anesthetics in mice. Both single short-term exposure and repeated exposure to halothane and nitrous oxide were studied. Exposure to 30% CO2 served as a positive control. Mortality, brain invasion, spleen weight, and antiviral antibodies served as the experimental endpoints. Halothane and nitrous oxide led to viral brain invasion, increased mortality, and suppressed immune response in a concentration- and time-dependent manner. Repeated exposures had a cumulative effect. Assessment of the stability of the viral attenuation did not demonstrate any alteration in the character of the virus, suggesting an increased access to the brain by inhalation anesthetics that led to the fatal encephalitis. These findings may be of special concern to populations at risk, such as operating room staff and patients undergoing general anesthesia in endemic areas of encephalitic virus species, in which subclinical infection may develop into an overt disease.
authors.affiliation: Laboratory for Research in Anesthesia, Pain and Neuroscience, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. ykatz18@hotmail.com
authors.forename: Yeshayahu
authors.initials: Y
authors.lastname: Katz
authors.forename: Shlomo
authors.initials: S
authors.lastname: Lustig
authors.forename: Izhar
authors.initials: I
authors.lastname: Ben-Shlomo
authors.forename: David
authors.initials: D
authors.lastname: Kobiler
authors.forename: David
authors.initials: D
authors.lastname: Ben-Nathan
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001921:Brain / Q000821:virology*; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D014774:Virulence; D014901:West Nile Fever / Q000276:immunology* / Q000401:mortality / Q000821:virology; D014902:West Nile virus / Q000187:drug effects / Q000472:pathogenicity*
chemical_list: D018685:Anesthetics, Inhalation; D000914:Antibodies, Viral; D009609:Nitrous Oxide; D006221:Halothane