Cyclosporine A inhibits TNF production without decreasing TNF mRNA levels

Biochem Biophys Res Commun. 1989 Jun 15;161(2):551-5. doi: 10.1016/0006-291x(89)92634-x.

Abstract

The role of cytokines in health and disease has received increasing attention and numerous investigations have explored the regulation of cytokine gene expression. Tumor necrosis factor-alpha (TNF) has received particular attention because of its central role in septic shock and more recent work has shown its participation in transplant immunology. We explored the mechanism of cyclosporine A (CsA) modulation of complete Freunds adjuvant macrophage (CFA-MO) TNF gene expression. From 0.001 to 1 microgram/ml, CsA dose-dependently inhibited lipopolysaccharide (LPS) induced secreted bioactivity; at doses above 10 micrograms/ml CSA was directly toxic to CFA-MO. However, there was no suppression of TNF mRNA levels, and CsA also did not inhibit the accumulation of cell-associated TNF. Thus, CsA modulates TNF gene expression in a previously undescribed manner.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Survival
  • Cyclosporins / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred CBA
  • RNA, Messenger / genetics
  • Solubility
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cyclosporins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha