THE INCREASED POTENTIAL FOR THE PRODUCTION OF INFLAMMATORY CYTOKINES BY KUPFFER CELLS AND SPLENIC MACROPHAGES 8 DAYS AFTER THERMAL-INJURY

Burn patients often experience a devastating inflammatory response to infection within the first two weeks after thermal injury. The inflamm atory cytokines IL-6, TNF and IL-1 have been implicated in this condit ion but most studies have focused on the abnormal levels of cytokines in the plasma. In this study the production of cytokines was compared for Kupffer cells versus splenic macrophages; endotoxin (LPS) stimulat ion versus no stimulation; and burn (post burn days 1, 3 and 8) versus no burn (control). Corresponding serum levels of IL-6 were also deter mined. Kupffer cells from normal or burned animals were shown to produ ce much higher amounts of the inflammatory cytokines than that produce d by splenic macrophages. An exception to this was the equal productio n of TNF by LPS-stimulated hepatic and splenic cells. Both LPS-stimula ted Kupffer cells and splenic macrophages produced larger amounts of t he cytokines than that produced by the unstimulated cells. There was a significant effect of thermal injury on cytokine production by LPS-st imulated Kupffer cells at post burn day 8 and on TNF production by sti mulated splenic macrophages also at post burn day eight. Although ther e was a statistically significant effect of thermal injury at post bur n day 8 on IL-1 production by unstimulated splenic macrophages, the ab solute amount of cytokine produced was very small. The results suggest that by post burn day 8 the cells may have become primed to respond t o a stimulus such as endotoxin (LPS), a condition that could arise in a burn patient from sepsis. Strangely, the large spike in serum IL-6 l evel occurred at post burn day one and the level of the cytokine retur ned nearly to the control value on post burn days 3 and 8.