Alterations in Splenic Lymphocyte Subpopulations and Increased Mortality from Sepsis Following Anesthesia in Mice

Abstract

The authors evaluated the potential of a variety of anesthestics in mice to produce subsequent alterations in host defenses. Specific monoclonal antibodies and immunofluorescent microscopy were used to enumerate splenic helper/inducer: suppressor/cytotoxic lymphocyte ratios (HSR) and resistance to bacterial challenge was evaluated by a cecal ligation and puncture (CLP) model. Two h of anesthesia with the i.v. agents ketamine and pentobarbital and with the inhalational agents isoflurane enflurane, halothane and halothane-NO2, were utilized. All anesthetics produced marked depression in the HSR, measured 24 h postanesthesia (P < 0.05); with all agents, helper T-cell populations were decreased and suppressor populations increased. The HSR remained depressed 72 h postanesthetic, following ketamine and halothane anesthesia (P < 0.05). A dose-response curve was determined with enflurane; increasing the anesthetic time from 1 to 6 h resulted in progressively greater depression of the HSR 24 h later. Changes in lymphocyte subtypes of similar magnitude were found in mice after burn injury or hind limb crush injury and amputation; simple laparotomy did not produce such changes. Serum corticosterone levels were unelevated 24 h post-anesthetic with enflurane, suggesting that the alterations were not nonspecific stress reactions. Resistance to sepsis was determined by measuring survival for 96 h after CLP. With CLP performed 24 h following 2 h anesthesia, mortality was increased from normal: control mortality 36.3%; ketamine 65.0% (P < 0.023); isoflurane 69.5% (P < 0.006); enflurane 84.2% (P < 0.0002). Anesthesia produces dose-related alterations in splenic helper/inducer and supressor/cytotoxic lymphocyte populations in mice, which persist for at least 72 h; resistance to subsequent bacterial challenge also is reduced, although the 2 effects are not proven to be related.