This project is based on the hypothesis that clarification of the mechanisms of immune dysfunction that occurs after thermal injury will ultimately lead to new therapeutic strategies which will improve patient survival.
The first aim i s to perform coordinated synchronous measurements of three distinct components of the immunological system (neutrophil chemotaxis and bactericidal activity, lymphocyte blastogenesis, and reticuloendothelial system reserve as reflected by circulating levels of cold insoluble globulin). Studies of the biologic effect of the soluble products of unstimulated and mitogen stimulated patient lymphocytes on control neutrophil chemotaxis and bactericidal activity will be performed, to determine if the depressed neutrophil function seen after thermal injury is related to suppressive lymphocyte activity.
The final aim of this project is to study the cellular steps of the chemotactic response in patients with impaired chemotaxis. This will be accomplished by breaking the chemotactic response down into its component steps (neutrophil adherence, cell-spreading, and ability of the neutrophil to orient towards a chemotactic gradient). The study group will be composed of 80 adult patients who have sustained thermal injury greater than 20 percent of the total body surface area. The patients will be stratified according to their predicted mortality rate by probit analysis, burn size, and by the presence or abscence of septic episodes. Although investigators have documented that abnormalities of neutrophil function, lymphocyte blastogenesis and cold insoluble globulin levels are each prognostically important in defining which patient will have septic complications, no studies have been performed measuring all these variables synchronously. Complete immunologic information is critical in the planning of potential immunomodulator therapy, since most immunomodulators have a broad spectrum of activity. Thus, the complete immunologic picture which will be generated by this study might help in deciding which immunomodulators would theoretically offer the best clinical benefits with the least clinical risk.
| Deitch, E A; Landry, K N (1986) Neutrophil subpopulations change after thermal injury. J Trauma 26:534-7 |
| Deitch, E A; Dobke, M; Baxter, C R (1985) Failure of local immunity. A potential cause of burn wound sepsis. Arch Surg 120:78-84 |
| Deitch, E A; Landry, K N; McDonald, J C (1985) Postburn impaired cell-mediated immunity may not be due to lazy lymphocytes but to overwork. Ann Surg 201:793-802 |
