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

作者：Takashi Ikejima, Seijiro Okusawa, Pietro Ghezzi, Jos W. M. van der Meer, Charles Anthony Dinarello · 发表于：The Journal of Infectious Diseases · 年份：1990 · DOI：10.1093/infdis/162.1.215 · 被引用次数：118 · 研究领域：Immune Response and Inflammation、Cytokine Signaling Pathways and Interactions、Pharmacological Effects of Natural Compounds

Recombinant human interleukin-1 (IL-1), injected into rabbits, induces the synthesis of endogenous 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-alpha (TNF-alpha) production by PBMC of 40 individuals stimulated with IL-1 alpha or IL-1 beta was determined by specific radioimmunoassay (RIA). After 3 h of PBMC incubation with IL-1, TNF-alpha mRNA was detected. IL-1 alpha stimulated both IL-1 beta and TNF-alpha, but there was no correlation in the amount of TNF-alpha or IL-1 beta synthesized in the PBMC of 29 individuals. IL-1-stimulated adherent cells produced approximately 50% more TNF-alpha than did unfractionated PBMC. Coincubation with interferon-gamma (IFN-gamma) did not change the amount of IL-1-induced TNF-alpha, whereas in the same culture IFN-gamma inhibited (greater than 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-1 alpha or -1 beta. These studies demonstrate that IL-1 induced TNF-alpha production in vivo and in vitro.