Factors involved in early in vitro endotoxin hyporesponsiveness in human endotoxemia

Sepsis and endotoxemia induce a state of early tolerance to the biological effects of endotoxin. Relatively little is known about the mechanisms or mediators involved in this endotoxin hyporesponsiveness. In this study endotoxin-induced TNF production of whole blood obtained at different time points from endotoxin challenged volunteers, and endotoxin- and PHA-induced TNF production by healthy PBMNCs in the presence of serum from endotoxin challenged volunteers were compared. Endotoxin-induced TNF production by whole blood was found to be significantly reduced at 2 h after in vivo endotoxin administration, returning to baseline levels at t = 6 h. In addition, a reduction of TNF produced by healthy PBMNCs in the presence of post-endotoxin serum was observed. No correlation was found with the concentration of any of the well described anti-inflammatory mediators investigated nor with plasma levels of endotoxin-binding proteins.