The action of interleukin 6 and leukaemia inhibitory factor on liver cells

Ciba Found Symp. 1992:167:100-14; discussion 114-24. doi: 10.1002/9780470514269.ch7.

Abstract

The hepatic action of cytokines has generally been analysed in terms of the acute-phase response of the liver. The qualitative and quantitative changes in the expression of plasma proteins serve as defining criteria for cytokine function. Interleukin 6 (IL-6) and leukaemia inhibitory factor (LIF) are representatives of a group of cytokines which display strikingly similar effects in both human and rodent liver cells. Hallmarks of the action of these cytokines are the stimulation of type 2 acute-phase plasma proteins and enhancement of the effect of interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF-alpha) on type 1 acute-phase plasma proteins. The transcriptional activation of the various acute-phase plasma protein genes involves common cis-acting regulatory elements whose sequences and location relative to the transcription start site vary from gene to gene. The activity of the IL-6- and LIF-responsive genes depends in part on transcription factors including several members of the C/EBP family, JunB and the glucocorticoid receptor. The expression of these transcription factors is in turn under cytokine-specific control. In a few cases, expression is temporally correlated with the activation of 'late' acute-phase protein genes. The finding that structurally distinct cytokines interact with separate receptors but elicit an almost identical liver cell response demands a reassessment of the contribution of each factor to the in vivo acute-phase response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Blood Proteins / drug effects
  • Cell Line
  • Growth Inhibitors / pharmacology*
  • Interleukin-6 / pharmacology*
  • Leukemia Inhibitory Factor
  • Liver / cytology
  • Liver / drug effects*
  • Lymphokines / pharmacology*
  • RNA, Messenger / drug effects
  • Transcription Factors / genetics
  • Transcription, Genetic / drug effects

Substances

  • Blood Proteins
  • Growth Inhibitors
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lymphokines
  • RNA, Messenger
  • Transcription Factors