IL-4 suppresses cytokine gene expression induced by IFN-gamma and/or IL-2 in murine peritoneal macrophages

J Immunol. 1992 Mar 15;148(6):1725-30.

Abstract

The effect of IL-4 on inflammatory gene expression in murine peritoneal macrophages stimulated with IFN-gamma in combination with IL-2 has been examined. These agents cooperatively induce the expression of mRNA for TNF-alpha and IP-10. Murine rIL-4 suppresses cytokine mRNA expression depending on the stimulus used and the mRNA being measured. Expression of TNF-alpha mRNA in macrophages stimulated with IFN-gamma, IL-2, or the combination is markedly suppressed by IL-4 whereas LPS-induced TNF-alpha mRNA is unaffected. In contrast, IP-10 mRNA expression is more sensitive to suppression by IL-4 when stimulated by LPS than by IFN-gamma/IL-2. IL-4-mediated suppression does not alter the time course of mRNA expression. Treatment of IFN-gamma/IL-2-stimulated macrophages with cycloheximide blocks the suppressive effect of IL-4, suggesting that de novo synthesis of an intermediate protein is part of the suppressive mechanism. The IL-4-mediated suppression of IFN-gamma/IL-2-driven TNF-alpha gene expression appears to be mediated at the level of transcription. These findings support a role for IL-4 as an antiinflammatory cytokine and suggest that macrophage inflammatory function will be dependent on the precise stimulus composition of the tissue microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Ascitic Fluid / cytology
  • Chemokine CXCL10
  • Chemokines, CXC*
  • Cycloheximide / pharmacology
  • Cytokines / genetics*
  • Gene Expression / drug effects
  • In Vitro Techniques
  • Interferon-gamma / pharmacology*
  • Interleukin-2 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Chemokine CXCL10
  • Chemokines, CXC
  • Cytokines
  • Interleukin-2
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma
  • Cycloheximide