Reduction of interleukin-17-induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin-4

Arthritis Rheum. 2000 Jun;43(6):1300-6. doi: 10.1002/1529-0131(200006)43:6<1300::AID-ANR12>3.0.CO;2-D.


Objective: To investigate the role of interleukin-4 (IL-4) and IL-10 in basal and IL-1- and IL-17-mediated inhibition of chondrocyte metabolism.

Methods: Cartilage explants of patellae from naive mice were incubated with IL-17 and/or IL-1 alone or were pretreated with IL-4 and IL-10. In addition, knee joints of naive mice were injected intraarticularly with IL-4 and IL-10 alone or were coinjected with IL-1. Chondrocyte proteoglycan (PG) synthesis was measured in intact murine articular cartilage. Levels of nitric oxide (NO) were measured using the Griess reagent.

Results: IL-17, a novel cytokine secreted by CD4+ activated memory T cells, inhibited chondrocyte PG synthesis in intact murine articular cartilage, although the suppressive effect was less potent than that of IL-1. The suppressive effect of IL-17 was completely abolished in the presence of L-NIO (L-NS-[1-iminoethyl]ornithine), an inhibitor of NO metabolism, and IL-17 only slightly induced inhibition of PG synthesis in cartilage explants of patellae from iNOS (inducible NO synthase) knockout mice. This indicates that the suppressive effect of IL-17 was mediated by NO. Pretreatment with IL-4, but not IL-10, significantly reduced the inhibition of chondrocyte PG synthesis induced by IL-1 or IL-17. The IL-4-induced reduction in the inhibitory effects of IL-1 and IL-17 on chondrocyte PG synthesis was accompanied by decreased NO formation in the culture supernatants.

Conclusion: IL-17 plays a role in the inhibition of chondrocyte PG synthesis. IL-4 and IL-10 have no effect on basal chondrocyte metabolism. However, IL-4-pretreated cartilage is less sensitive to the suppressive effect of IL-1 as well as IL-17. This suggests that IL-4 is protective in T cell-driven cartilage disturbances, probably through reduction of iNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism*
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Culture Techniques
  • Female
  • Interleukin-1 / pharmacology
  • Interleukin-10 / pharmacology
  • Interleukin-17 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / physiology
  • Patella
  • Proteoglycans / antagonists & inhibitors*
  • Proteoglycans / biosynthesis


  • Interleukin-1
  • Interleukin-17
  • Proteoglycans
  • Interleukin-10
  • Interleukin-4
  • Nitric Oxide