CYTOKINE KINETICS IN AN INVITRO WHOLE-BLOOD MODEL FOLLOWING AN ENDOTOXIN CHALLENGE

Whole blood and peripheral blood mononuclear cell (PBMC) culture model s have been used to study cytokine stimulation and release in vitro. I n this study, we characterize the kinetics of the interleukins (IL-1be ta), (IL-6), (IL-8), and tumor necrosis factor-alpha (TNF-alpha) follo wing an endotoxin (ET) challenge using our in vitro whole blood model. Whole blood samples from 10 healthy volunteers were studied. All cyto kines were measured by enzyme-linked immunosorbent assay. Peak concent rations of TNF-alpha occurred 2 h after ET challenge followed by a rap id decline in free plasma TNF-alpha concentration (half-life 18.2 min) . IL-1beta was not significantly elevated until 4 h after ET challenge . IL-8 was elevated 1 h after ET challenge. IL-6 concentration exhibit ed a biphasic peak occurring at 6 and 74 h after ET challenge. We conc lude that (1) our whole blood in vitro model produces cytokine release kinetics similar to those reported in vivo, and (2) the presence of e ither binding proteins or cellular metabolism of TNF-alpha. in whole b lood produces a similar plasma half-life to that observed in vivo.