INCREASED CIRCULATING CYTOKINES, CYTOKINE ANTAGONISTS, AND E-SELECTINAFTER INTRAVENOUS ADMINISTRATION OF ENDOTOXIN IN HUMANS

Intravenous administration of endotoxin into humans causes transient f ever, alteration in the number of circulating neutrophils, and transie nt release into plasma of cytokines, cytokine antagonists, and other c ellular products. The release can be temporally differentiated, and th e extent of release is dose-dependent. By 1 h after endotoxin challeng e, levels of tumor necrosis factor (TNF)-alpha and soluble TNF recepto r increase; interleukin (IL)-6 and IL-8 increase by 1.5 h, and IL-1 re ceptor antagonist, granulocyte colony-stimulating factor (G-CSF), gran ulocyte-macrophage colony-stimulating factor, and lactoferrin increase by 2 h. Increased G-CSF is temporally associated with neutrophilia an d the appearance of band neutrophils. Increased plasma lactoferrin and altered neutrophil surface antigen expression suggest that intravascu lar activation of neutrophils has occurred. The level of soluble E-sel ectin (sE-sel), an adhesion molecule released from endothelial cells, is elevated at 4 h and remains elevated at 24 h. sE-sel levels increas e with higher doses of endotoxin at 4, 6, and 24 h.