Interleukin-4 differentially regulates tumor necrosis factor-alpha gene expression by human T lymphocytes and monocytes

Pathobiology. 1992;60(2):100-7. doi: 10.1159/000163706.

Abstract

Tumor necrosis factor-alpha (TNF-alpha), a product of both mononuclear phagocytes and T lymphocytes, is an important proximal mediator of a number of acute and chronic inflammatory disease states. In this investigation we examine the regulatory effects of the lymphocyte product interleukin-4 (IL-4) on the gene expression of TNF-alpha from stimulated human peripheral blood monocytes (PBM) and T lymphocytes. We demonstrated the dose-dependent suppression of TNF-alpha mRNA and protein synthesis from lipopolysaccharide-treated PBM by IL-4. The suppressive effects of IL-4 appear to be dependent upon de novo protein synthesis, as cycloheximide abrogated the IL-4-induced reduction in TNF-alpha mRNA levels from PBM. In contrast to the suppressive effects of IL-4 on PBM-derived cytokine expression, IL-4 did not alter TNF-alpha mRNA expression from alpha-Cd3 or PMA + alpha-CD-28-treated T lymphocytes. Moreover, IL-2 mRNA expression from similarly treated T lymphocytes was unaltered by IL-4. Our findings demonstrate that disparity exists in the regulation of TNF-alpha gene expression from different immune cell populations which may have important implications in the evolution of acute and chronic inflammatory responses.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cycloheximide / pharmacology
  • Depression, Chemical
  • Endotoxins / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-4 / pharmacology*
  • Leukocytes, Mononuclear / drug effects*
  • Lymphocyte Activation
  • Molecular Sequence Data
  • RNA, Messenger / biosynthesis
  • T-Lymphocytes / drug effects*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Endotoxins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Cycloheximide