Immunomodulation by Agents Which Inhibit Suppressor Cells in Injured Mice

摘要

We have completed extensive studies on immune downregulation after defined injury in mice. We employed a standard model of musculoskeletal injury, crush injury of the hind limb coupled with immediate limb amputation, which has been shown by other groups to lead to immune suppression and to the generation of suppressor cells. We compared immunity in these animals to immunity in animals receiving a moderate-sized full-thickness burn injury. Studies showed that implantation of burned tissue or devitalized, nonburned skin or other tissue into normal mice via a subcutaneous pocket recreated all of the immune dysfunctions seen after burn injury. We suspect therefore that immune dysfunction after injury may result from an amplified local host response to devitalized tissue; this may involve elements of the inflammatory response. Further work has sought to identify potential mediators of immune dysregulation after injury or stress. We studied the effects of catecholamines, prostaglandins, and histamines, since all three mediators are increased after injury. Studies suggest that devitalized tissue contributes to immune downregulation after injury, and that circulating or tissue mediators which have been shown to be elevated after injury may contribute to immune dysfunction after injury.