Hypothermia attenuates beta 1 integrin expression on extravasated neutrophils in an animal model of meningitis

Brain injury in meningitis occurs in part as a consequence of leukocyte mig ration and activation. Leukocyte integrins are pivotal in the inflammatory response by mediating adhesion to vascular endothelium and extracellular ma trix proteins. We have demonstrated that moderate hypothermia early in the course of meningitis decreases leukocyte sequestration within the brain par enchyma. This study examines whether hypothermia alters neutrophil integrin expression in a rabbit model of bacterial meningitis. Prior to the inducti on of meningitis, peripheral blood samples were obtained and the neutrophil s isolated. Sixteen hours after inducing group B streptococcal meningitis, animals were treated with antibiotics, IV fluids, and mechanically ventilat ed. Animals were randomized to hypothermia (32-33 degreesC) or normothermia conditions. After 10 hours of hypothermia or normothermia, neutrophils wer e isolated from the blood and cerebral spinal fluid (CSF), stained for beta 1 and beta2 integrins, and analyzed using flow cytometry. Cerebral spinal f luid neutrophil beta1 integrin expression was significantly decreased in hy pothermic animals. Beta-1 integrins can assume a higher affinity or "activa ted" state following inflammatory stimulation. Expression of "activated" be ta1 integrins was also significantly decreased in hypothermic animals. Beta 2 CSF neutrophil integrin expression was decreased in hypothermic animals, but failed to reach significance. These data suggest hypothermia may attenu ate extravasated leukocyte expression of both total and "activated" beta1 i ntegrins.