Research Project
3436640
Disorders of polymorphonuclear neutrophil (PMN) functions appear to be the major predisposing factor to the development of sepsis in burn patients and other clinical settings. Thus, repair of PMN function in these infection-prone patients is of primary importance. With the development of several synthetic immunopotentiators and the availability of several human lymphokines as a result of recombinant DNA technology, it is now possible to screen several agents for their ability to stimulate neutrophil function. It is of primary importance to determine if effects on PMN function correlate with increased resistance to bacterial infection. The model system to be used is the burned mouse model and resistance to two agents, Pseudomonas aeruginosa and Listeria monocytogenes, will be determined following treatment with immunomodulators. The effect of NPT 15392, a synthetic inosine derivative which has been shown to affect lymphocyte, NK cell, and monocyte function, and Tumor Necrosis Factor, which has recently been shown to enhance tumor cytotoxicity function of human PMNs, will be studied. If an immunopotentiator affects the ability of neutrophils to kill bacteria, plans include determination of the effect of the agent on the oxygen-dependent and oxygen-independent killing mechanisms of PMNs. If effective modulation of PMN function can be established in vitro and in the burned mouse model, it would be the long-range goal to determine the effect of these immunopotentiators in intact individuals and in patients with granulocyte dysfunction.
