Kinetics of interleukin-2 and interleukin-6 synthesis following major mechanical trauma

Abstract

Although it is known that mitogen-induced lymphocyte proliferation and interleukin-2 (IL-2) synthesis are depressed following mechanical trauma, it is not known whether these defects are due to high levels of circulating prostaglandin E 2 released by macrophages, suppressor T-lymphocytes, and serum suppressive factors or due to intracellular defects in T-lymphocytes. Moreover, the kinetic of interleukin-6 (IL-6), a new multifunctional cytokine, following trauma is not known. To study this, highly purified T-cell cultures were prepared from 21 patients with major mechanical trauma on Days 3, 7, 10, 14, and 21 post-trauma and assayed for proliferative response to phytohemagglutinin, IL-2, and IL-6 synthesis. T-lymphocyte proliferation of patients was unaltered on all days post-trauma compared to that of healthy controls. Interleukin-2 synthesis of patients showed a significant ( P < 0.01) reduction ranging from 23% of control values on Day 3 to 40% on Day 21. Interleukin-6 synthesis in contrast was markedly increased ( P < 0.05) in the patient group on all days up to sixfold (Day 3) with a tendency toward normalization on Day 21. High levels of IL-6 correlated with the appearance of infectious complications in the post-traumatic course. These data indicate that the alterations in T-cell proliferation and IL-2 synthesis following major injury found in earlier studies are caused by different suppressor mechanisms. While T-cell proliferation is only decreased by extracellular components, IL-2 synthesis is suppressed mainly by an intracellular defect. The role of highly increased IL-6 levels and its effect on the immune response are so far unknown.