Effect of combined cortisol-endotoxin administration on peripheral blood leukocyte counts and phenotype in normal humans
S. E. Calvano, A. E. Barber, A. S. Hawes, H. F. de Riesthal, S. M. Coyle and S. F. Lowry
Department of Surgery, Cornell University Medical College, New York, NY.
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.