Both proliferative and phenotypic data from our laboratory suggest that a predominant feature of burn-induced immunodeficiency is an alteration in the number and/or function of Interleukin-2 producing OKT-4+ lymphocytes. The purpose of this research project is to characterize the cellular and molecular cell-membrane events associated with the immunomodulatory and immunotherapeutic effects of Interleukin-2 and other lymphokines, following thermal injury in humans and in the burned animal model. The long term objectives include the organization of immunotherapeutic regimens designed to supplement specific injury- or septic-related immunologic deficits. The experimental design of this project will document any alteration in the absolute number and percentage of lymphocyte subpopulations expressing the phenotype for specific functionally active immune cells by fluorescence flow cytometry, and correlate any change in phenotype with proliferative, functional and lymphokine production immune defects. Specific microassays for Interleukin-1 and Interleukin-2 will be used to simultaneously quantify their production. Correlation of abnormalities in activation antigen expression with cell cycle kinetics and lymphokine production may allow identification of the molecular determinants of immunodeficiency. Once the level(s) of the defect(s) is(are) identified, it may be possible to bypass the defect and restore function in vivo. The animal model will allow complete investigation of in vivo manipulation of single and combination putative immunotherapeutic lymphokines and offers a method for testing the clinical efficacy of various treatment modalities in the setting of burn wound sepsis.
