Dose-dependence of bacterial lipopolysaccharide (LPS) effects on peak response and time course of the immune-endocrine host response in humans

Objective and Design: Dose-dependence of lipopolysaccharide (LPS) effects on peak and time course parameters of the immune-endocrine host response was examined in a placebo-controlled design. Subjects: Data from 42 male volunteers were included. Treatment: 0.4 or 0.8 ng LPS/kg body weight were applied at 7.00 p.m. Methods: Body temperature, heart rate and leukocyte counts were quantified. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), cortisol and human growth hormone (hGH) were measured. Results: LPS increased significantly the levels of immune (TNF-alpha, IL-6) and endocrine (ACTH, cortisol) parameters. HGH secretion was advanced without changes in the total amount of hGH released. Dose-dependence of endotoxin's effects was significant for neuroendocrine (cortisol) and physiological (temperature, heart rate) parameters. Examination of time course parameters demonstrated that the higher dose of endotoxin prolonged the increases in temperature, IL-6 and cortisol levels. Conclusions: Our data show that increases in the dosage of LPS lead to differential peak responses and changed time course patterns of the human host response.