REGULATION OF INTERLEUKIN-1 GENERATION IN IMMUNE-ACTIVATED FIBROBLASTS

In the present study we have demonstrated that fibroblasts can generate the inflammatory cytokine interleukin 1 (IL 1) under conditions similar to those abundant in cellular immune responses. Thus, induction of IL 1 requires a sequential two‐step protocol which consists of preactivation of mouse embryo fibroblasts (MEF) with crude preparations of T cell or macrophage‐derived conditioned media (CM; 72 h), followed by a challenge with lipopolysaccharide (LPS; 24 h). Unstimulated fibroblasts or such cells activated by either CM or LPS produced only low levels of IL 1, while a synergism between both signals was observed for obtaining maximal IL 1‐like activity in MEF. Each of a series of individual recombinant lymphokines and cytokines (IL 2, granulocyte/macrophage‐colony‐stimulating factor, tumor necrosis factor, IL 1β and interferons‐α, β and γ) was shown to serve as an efficient priming signal for the induction of IL 1. IL 1‐like activity in fibroblasts was detected in cell lysates or associated with the producing‐cell membrane but not in culture fluids. Immune‐stimulated fibroblasts, activated under such experimental conditions, were shown to actively transcribe mRNA of both IL 1 genes (α and β). For the expression of IL 1‐specific mRNA in fibroblasts a single stimulus, provided by either LPS or a lymphokine/cytokine, was sufficient; however, a more intense signal was observed when both stimuli were applied. The IL 1‐like biological activity of fibroblast origin was significantly reduced by anti‐IL 1α antibodies. Thus, fibroblasts, when activated by immune and bacterial products, generate IL 1 which in turn possibly amplifies cellular immune responses or inflammatory processes in connective tissues. Copyright © 1990 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim