Halothane Inhibits the Intraalveolar Recruitment of Neutrophils, Lymphocytes, and Macrophages in Response to Influenza Virus Infection in Mice

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The effect of halothane anesthesia on the influenza A specific immune response and the pathogenesis of infection was evaluated in mice. Three-wk-old CD-1 mice were anesthetized with either 2% halothane for 2 h or ketamine (100 mg/kg intraperitoneally) and subsequently inoculated intranasally with a sublethal dose of influenza type A/PR/8/34 virus. Bronchoalveolar lavage was performed on animals from each group at 4 h postinoculation and daily thereafter for 14 days. Total and differential white blood cell counts were measured in the lavage fluid and the lungs were examined histologically for evidence of injury. Infected mice anesthetized with halothane had lower daily cell counts in the lung than animals anesthetized with ketamine and a marked change in cell type distribution. On Days 4 and 11 postinoculation, there were significantly (P < 0.05) more white blood cells in the lavage fluid of animals anesthetized with ketamine than halothane (mean/mL, 738,000 ± SEM, 128,000 vs 196,000 ± 51,400, respectively, and 1,020,000 ± 227,000 vs 117,000 ± 34,600, respectively). Differential counts were significantly higher (P < 0.05) in the ketamine group compared to the halothane for neutrophils on Day 4 (452,000 ± 77,900 vs 72,000 ± 46,000, respectively) and on Day 11 for lymphocytes (340,000 ± 59,000 vs 33,000 ± 17,000, respectively) and macrophages (480,000 ± 120,000 vs 130,000 ± 61,000). Infected mice that were given ketamine were qualitatively “sicker” than the halothane-treated group as evidenced by the appearance of ruffled fur, tachypnea, and cachexia. Animals anesthetized with ketamine demonstrated a greater degree of pulmonary histopathology including diffuse infiltration of macrophages, neutrophils, hemorrhage, and fibrin deposition. There was, however, no difference in cumulative mortality between the two groups for up to 21 days postinoculation. This study supports the hypothesis that halothane anesthesia decreases the pathogenesis of influenza virus pneumonitis in mice by suppressing the local recruitment of individual alveolar immunocytes.

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