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.

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.

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‐N⁵‐[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.

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.