INTERLEUKIN-1-BETA AND INTERFERON-GAMMA REGULATE INTERLEUKIN-6 PRODUCTION IN CULTURED HUMAN INTESTINAL EPITHELIAL-CELLS

Recent studies suggest that interleukin-6 (IL-6) is produced in the in testinal mucosa during sepsis and endotoxemia and that the enterocyte may be a source of IL-6 in these conditions. The regulation of IL-6 pr oduction in the enterocyte is not fully understood. We tested the hypo thesis that IL-6 production in the enterocyte is regulated by proinfla mmatory cytokines. This was done by treating cultured Caco-2 cells, a transformed human intestinal epithelial cell line, with different conc entrations of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6 or interferon-gamma (IFN-gamma). IL-6 production by the Caco-2 cells was determined by ELISA. The expression of IL-6 mRNA was determined by reverse-transcriptase polymerase chain reaction. IL-6 was not produce d in unstimulated Caco-2 cells. Treatment of the Caco-2 cells with IL- 1 beta resulted in a dose-and time-dependent stimulation of IL-6 produ ction with a maximal effect noted at an IL-1 beta concentration of .5 ng/mL at 24 h. IFN-gamma alone did not stimulate IL-6 production but p otentiated the effect of IL-1 beta in a synergistic fashion. Treatment of the Caco-2 cells with IL-1 beta induced expression of IL-6 mRNA wi th a response noticed after 30 min. TNF-alpha and IL-6 did not influen ce the production of IL-6 in the Caco-2 cells. The results suggest tha t enterocyte IL-6 production is stimulated by IL-1 beta and that this effect is potentiated by IFN-gamma. The regulation of IL-6 production in the enterocyte may be specific for IL-1 beta, since neither TNF nor IL-6 stimulated IL-6 production.