Mechanisms of action of two new immunomodulators
J. P. Waymack, S. Gonce, P. Miskell and J. W. Alexander
Despite antibiotics, infection remains a significant problem in surgical
patients. The reasons are multiple, and include acquired immunologic
deficiencies that are seen in malnutrition, sepsis, trauma, and burns. Two
immunomodulators, thymopentin (TP-5) and CP-46,665, have been shown to
improve survival in infectious animal models of such deficiencies. We
investigated the mechanism of action in guinea pigs subjected to a burn of
30% of the total body surface area. These animals received 0.3 mg/kg of
thymopentin, 0.3 mg/kg of CP-46,665, or saline solution. Neutrophils,
macrophages, and serum samples were obtained from the animals and tested
for their ability to phagocytose and kill Pseudomonas aeruginosa. The serum
was tested for its ability to opsonize Escherichia coli. Thymopentin was
found to improve neutrophil function on postburn days 2 and 4 and to
improve macrophage function on postburn day 4. CP-46,665 was found to
improve both macrophage function and opsonization on postburn day 2.
