Interleukin-l Induces Tumor Necrosis Factor (TNF) in Human Peripheral Blood Mononuclear Cells In Vitro and a Circulating TNF-Iike Activity in Rabbits

Publisher Website
Google Scholar
Abstract
Recombinant human interleukin-1 (IL-1), injected into rabbits, induces the synthesis ofendogenous IL-1. Also, IL-1 induces its own gene expression and synthesis in human peripheral blood mononuclear cells (PBMC). In this study, tumor necrosis factor-α (TNF-α) production by PBMC of 40 individuals stimulated with IL-1α or IL-1β was determined by specific radioimmunoassay (RIA). After 3 h ofPBMC incubation with IL-1, TNF-α mRNA was detected. IL-la stimulated both IL-1β and TNF-α, but there was no correlation in the amount of TNF-α or IL-1β synthesized in the PBMC of 29 individuals. IL-1-stimulated adherent cells produced ∼50% more TNF-α than did unfractionated PBMC. Coincubation with interferon-v (IFN-γ) did not change the amount of IL-l-induced TNF-α, whereas in the same culture IFN-γ inhibited (>70%) IL-1-induced IL-1 production. Endogenous pyrogen and TNF-like activity were detected in the sera of rabbits 3.5 h after injection of either IL-1α or -1β. These studies demonstrate that IL-l induced TNF-α production in vivo and in vitro.