Interleukin 1 and tumor necrosis factor‐α additively increase the levels of granulocyte‐macrophage and granulocyte colony‐stimulating factor (CSF) mRNA in human fibroblasts

Abstract

Abstract Recombinant interleukin (IL) 1 β and tumor necrosis factor/cachectin (TNF‐α) induce, usually within 2 h, a dose‐dependent increase in the levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and G‐CSF mRNA in cultured human fibroblasts. Maximal induction is reached at about 4–8 h and usually last for at least 48 h. IL 1β and TNF have additive effects on the levels of GM‐ and G‐CSF mRNA, and on the secretion of G‐CSF activity into the culture medium. IL 1α has the same additive effect that IL 1β has with TNF, but no additive effect with IL 1β. In contrast, the high basic level of M‐CSF (CSF‐1) mRNA shows little or lower variations in response to IL 1, TNF‐α or both IL 1 and TNF‐α also induce, with similar kinetics, an increase in IL 1β but not mRNA level. In contrast to what is observed with macrophages and endothelial cells, E. coli lipopolysaccharide does not modify the fibroblast CSF mRNA level up to 48 h of culture.