Insulin-like growth factor-1 activity is inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6

Lymphokine Cytokine Res. 1993 Aug;12(4):219-23.


With evidence that several proteins inhibit insulin-like growth factor (IGF) activity, we evaluated whether cytokines, which are elevated in many catabolic states, also affect IGF-1-mediated proteoglycan synthesis. Cartilage from hypophysectomized rats was exposed to the cytokines interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) in the presence or absence of IGF-1. IL-1 alpha inhibited IGF-1-stimulated proteoglycan (PG) synthesis > 95% at 20 ng/ml (p < 0.01). TNF-alpha and IL-6 caused a maximum inhibition of 56 and 54%, respectively, both at 200 ng/ml. Only in the absence of IGF-1 did IL-1 alpha inhibit PG synthesis below unstimulated levels, suggesting that although IL-1 alpha can directly inhibit PG synthesis, IL-1 alpha, TNF-alpha, TNF-alpha, and IL-6 each promotes cartilage loss also by inhibiting IGF-1-mediated anabolism.

Publication types

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

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Humans
  • Hypophysectomy
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / pharmacology*
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / pharmacology*
  • Kinetics
  • Male
  • Mice
  • Organ Culture Techniques
  • Proteoglycans / biosynthesis*
  • Rats
  • Rats, Inbred F344
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Interleukin-1
  • Interleukin-6
  • Proteoglycans
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Insulin-Like Growth Factor I