The proposed training program is designed to facilitate the ability of Dr. Edward Sherwood to develop an independent and productive research career in the area of injury-induced immunosuppression. The training goals of the project are to: 1) provide didactic training in cellular and molecular immunology as well as the pathophysiology of trauma and burns; 2) develop the technical and scientific skills necessary to conduct high quality research and 3) generate data to test the proposed hypotheses and form the foundation for future competitive grant applications and publications. He will be mentored by Professors Daniel Traber and Frank Schmalstieg, experienced investigators in the field of burn injury who have an extensive record of training young investigators. The proposed research project is designed to characterize and treat burn-induced immunosuppression. Thermal injury results in the induction of type 2 T cells that secrete immunosuppressive cytokines. Evidence indicates that lack of IL- 12 secretion is largely responsible for the predominance of type 2 T cells in burned patients. IL-12 and IL-18 are cytokines that stimulate the production of immunopotentiating type 1 T cells. Evidence indicates that administration of IL-12 to thermally- injured mice will promote type 1 T cell predominance and enhance resistance to infection. Our preliminary studies show that glucan is a potent promoter of the production of IL-12 and the type 1 cytokine interferon gamma (IFNgamma). The proposed studies are based on the hypotheses that: 1. IL-12 and IL-18 secretion and function are impaired following thermal injury resulting in the predominance of type 2 T cells; 2. Administration of IL-12 and IL-18 to thermally injured mice will promote type l cytokine expression and enhance resistance to infection; 3. Administration of glucan to thermally injured mice will promote IL-12, IL-18 and IFNgamma production, increase type 1 T cell predominance and enhance resistance to infection.
