Evidence that interleukin-1, but not interleukin-6, affects costochondral chondrocyte proliferation, differentiation, and matrix synthesis through an autocrine pathway

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Abstract
Although the effects of interleukin‐1 (IL‐1) and interleukin‐6 (IL‐6) on articular cartilage chondrocytes have been reported, little is known concerning the effects of these cytokines on growth plate chondrocytes. In this study, we examined the effect of IL‐1α, IL‐1β, and IL‐6 on growth plate chondrocyte proliferation, differentiation, and matrix production as a function of cell maturation and examined the ability of these cells to produce IL‐1α and IL‐1β. Confluent fourth passage cultures of rat costochondral resting zone and growth zone chondrocytes were treated with 0–100 ng/ml of IL‐1α, IL‐1β, or IL‐6 for 24 h and then assayed for [3H]‐thymidine incorporation, alkaline phosphatase specific activity, [35S]‐sulfate incorporation, and percent collagen production. Neutralizing polyclonal antibodies were used to confirm the specificity of response to each cytokine. Treatment of resting zone cells with IL‐1α produced a significant, dose‐dependent decrease in [3H]‐thymidine incorporation, while similarly treated growth zone cells were unaffected by treatment with this cytokine. IL‐1α also stimulated alkaline phosphatase specific activity and inhibited [35S]‐sulfate incorporation by resting zone chondrocytes, but had no affect on growth zone chondrocytes. When collagen production was examined, it was observed that IL‐1α had a stimulatory affect on growth zone cells but no affect on resting zone cells. When the effect of IL‐1β was examined, it was observed that this cytokine inhibited [3H]‐thymidine incorporation by resting zone cells and stimulated isotope incorporation in growth zone cells. IL‐1β also stimulated alkaline phosphatase specific activity and inhibited [35S]‐sulfate incorporation by resting zone chondrocytes but had no affect on growth zone chondrocytes. In contrast to IL‐1α, IL‐1β stimulated collagen production by resting zone cells but not growth zone cells. IL‐6 had no affect on any of the parameters measured in either cell type. When cytokine production was measured, it was found that IL‐1α was produced by both cell types, while IL‐1β was produced only by resting zone cells. Resting zone cells secreted both IL‐1α and IL‐1β into the media, but 75% of the total cytokine produced by these cells was retained in the cell layer. In contrast, growth zone cells did not secrete measurable IL‐1α into the media. These results suggest that IL‐1α and IL‐1β target resting zone cells, inducing them to differentiate and acquire a phenotype characteristic of the more mature growth zone cells. Moreover, resting zone chondrocytes produce both IL‐1α and IL‐1β, suggesting the possibility of an autocrine effect of these cytokines on the cells.
Funding Information
  • NIH (DE-08603 and DE-05937)

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