• We studied the role of lipopolysaccharide and the associated hypercortisolemic response as mediators of leukocyte changes associated with endotoxemia. Normal human subjects were given continuous, 12-hour, intravenous infusions of cortisol. After 6 hours of cortisol infusion, lipopolysaccharide (20 U/kg) was administered in an intravenous bolus. Plasma cortisol and blood leukocyte counts and lymphocyte subset proportions were evaluated every hour throughout the 12-hour study period. After 6 hours of cortisol infusion, lymphocyte counts and proportions of CD4+ helper/inducer T cells had declined significantly. The fact that these cells did not decline further in response to lipopolysaccharide and continued cortisol infusion suggests that lipopolysaccharide-induced lymphocyte changes are cortisol dependent. In contrast, the granulocytosis normally observed after lipopolysaccharide administration was unaffected by cortisol infusion. Finally, the monocyte counts and proportions of B cells (HLA-DR+ or CD20+ cells) responded to cortisol infusion and LPS in a pattern distinct from that of lipopolysaccharide alone. These results indicate that lipopolysaccharide-induced hypercortisolemia plays a role in immune modulation during endotoxemia.
(Arch Surg. 1992;127:181-186)