In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-related differences

Ann Rheum Dis. 1994 Sep;53(9):593-600. doi: 10.1136/ard.53.9.593.

Abstract

Objectives: Transforming growth factor-beta (TGF-beta) has been shown to antagonise interleukin-1 (IL-1) effects in different systems. Investigations were carried out to study whether TGF-beta 1 modulates IL-1 induced inflammation and IL-1 effects on articular cartilage in the murine knee joint.

Methods: IL-1, TGF-beta 1 or both factors together were injected into the knee joint. Inflammation was studied in whole knee histological sections. Patellar cartilage proteoglycan synthesis was measured using 35S-sulphate incorporation while patellar cartilage glycosaminoglycan content was determined with automated image analysis on joint sections.

Results: Co-injection of TGF-beta 1 and IL-1 resulted in synergistic attraction of inflammatory cells. In contrast, TGF-beta 1 counteracted IL-1 induced suppression of articular cartilage proteoglycan synthesis. Proteoglycan depletion was similar shortly after the last injection of IL-1 or IL-1/TGF-beta 1, but accelerated recovery was found with the combination at later days. This protective effect of TGF-beta 1 could not be demonstrated in older mice.

Conclusions: TGF-beta 1 aggravates IL-1 induced knee joint inflammation, but counteracts the deleterious effects of IL-1 on articular cartilage proteoglycan synthesis and content. The data indicate that TGF-beta 1 could play an important part in articular cartilage restoration after IL-1 induced proteoglycan depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Cartilage, Articular / metabolism*
  • Drug Synergism
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Patella / metabolism
  • Proteoglycans / metabolism
  • Recombinant Proteins / pharmacology
  • Synovitis / etiology
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Interleukin-1
  • Proteoglycans
  • Recombinant Proteins
  • Transforming Growth Factor beta