Interleukin-1 beta and interferon-gamma regulate interleukin-6 production in cultured human intestinal epithelial cells

Shock. 1997 Oct;8(4):249-55. doi: 10.1097/00024382-199710000-00003.


Recent studies suggest that interleukin-6 (IL-6) is produced in the intestinal mucosa during sepsis and endotoxemia and that the enterocyte may be a source of IL-6 in these conditions. The regulation of IL-6 production in the enterocyte is not fully understood. We tested the hypothesis that IL-6 production in the enterocyte is regulated by proinflammatory cytokines. This was done by treating cultured Caco-2 cells, a transformed human intestinal epithelial cell line, with different concentrations 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 produced 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 production 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 potentiated 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 with a response noticed after 30 min. TNF-alpha and IL-6 did not influence the production of IL-6 in the Caco-2 cells. The results suggest that 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Caco-2 Cells
  • Humans
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology*
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology*
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Interleukin-6 / pharmacology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism*
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured


  • Adjuvants, Immunologic
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Interferon-gamma