Hypothermia attenuates beta1 integrin expression on extravasated neutrophils in an animal model of meningitis.

Abstract

Brain injury in meningitis occurs in part as a consequence of leukocyte migration and activation. Leukocyte integrins are pivotal in the inflammatory response by mediating adhesion to vascular endothelium and extracellular matrix proteins. We have demonstrated that moderate hypothermia early in the course of meningitis decreases leukocyte sequestration within the brain parenchyma. This study examines whether hypothermia alters neutrophil integrin expression in a rabbit model of bacterial meningitis. Prior to the induction of meningitis, peripheral blood samples were obtained and the neutrophils isolated. Sixteen hours after inducing group B streptococcal meningitis, animals were treated with antibiotics, IV fluids, and mechanically ventilated. Animals were randomized to hypothermia (32–33°C) or normothermia conditions. After 10 hours of hypothermia or normothermia, neutrophils were isolated from the blood and cerebral spinal fluid (CSF), stained for β1 and β2 integrins, and analyzed using flow cytometry. Cerebral spinal fluid neutrophil β1 integrin expression was significantly decreased in hypothermic animals. Beta-1 integrins can assume a higher affinity or "activated" state following inflammatory stimulation. Expression of "activated" β1 integrins was also significantly decreased in hypothermic animals. Beta2 CSF neutrophil integrin expression was decreased in hypothermic animals, but failed to reach significance. These data suggest hypothermia may attenuate extravasated leukocyte expression of both total and "activated" β1 integrins.