Effect of anesthetics on pathogenesis of experimentally induced murine pneumococcal pneumonia

Background and Purpose: To define the effects of three commonly used anesthetic agents - sodium pentobarbital given intraperitoneally, and inhaled halothane and methoxyflurane - on the pathogenesis of pneumococcal pneumonia and bacteremia in an experimental murine model. Methods: Swiss outbred mice were anesthetized with either sodium pentobarbital, halothane, or methoxyflurane before intranasal infection with Streptococcus pneumonia. At defined times after infection, bacterial numbers in lungs and blood, markers of acute lung injury, and lung cytokine levels were compared. Results: Mice anesthetized with inhaled halothane or methoxyflurane prior to intranasal inoculation with type-2 Streptococcus pneumoniae developed pneumonia and bacteremia distinctly different from that in mice anesthetized by intraperitoneal (IP) administration of sodium pentobarbital. Mice having brief exposure to inhaled halothane or methoxyflurane had significantly greater numbers of bacteria in lungs and blood 48 hours after inoculation, compared with mice anesthetized by IP administration of pentobarbital. Also, mice inhaling halothane had significantly decreased activities of pro- inflammatory cytokines interleukin 6 and tumor necrosis factor-α in lung homogenates at 24 hours after inoculation, compared with those given pentobarbital IP. Conclusion: Effects of anesthesia on murine models of pneumonia should be considered in the design and interpretation of studies of pneumococcal pathogenesis.