The superficial layer of human articular cartilage is more susceptible to interleukin‐1–induced damage than the deeper layers

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<jats:title>Abstract</jats:title><jats:p><jats:italic>Objective</jats:italic>. To compare the responses of chondrocytes from superficial and deep layers of normal human articular cartilage to interleukin‐1 (IL‐1) and IL‐1 receptor antagonist protein (IRAP), and to evaluate the binding sites for IL‐1 on these cells.</jats:p><jats:p><jats:italic>Methods</jats:italic>. Cartilage and chondrocytes from superficial and deeper layers of human femoral condyles were cultured with and without IL‐1 in the presence and absence of IRAP. The effect of these agents on <jats:sup>35</jats:sup>S‐proteoglycan synthesis and catabolism and production of stromelysin and tissue inhibitor of metalloproteinases 1 (TIMP‐1) were measured by biochemical and immunologic assays. Receptor binding was evaluated using <jats:sup>125</jats:sup>I‐labeled IL‐1.</jats:p><jats:p><jats:italic>Results</jats:italic>. IL‐1 induced more severe inhibition of proteoglycan synthesis and a lower ratio of secreted TIMP‐1:stromelysin in chondrocytes from superficial cartilage than those from deeper cartilage. IRAP blocked responses to IL‐1 more effectively in chondrocytes from deep cartilage than those from superficial cartilage. Chondrocytes from the articular surface showed approximately twice the number of high‐affinity binding sites for IL‐1 as did cells from deep cartilage.</jats:p><jats:p><jats:italic>Conclusion</jats:italic>. Chondrocytes from the surface of articular cartilage show a greater vulnerability to the harmful effects of IL‐1 and are less responsive to the potential therapeutic effects of IRAP than cells in the deeper layers of the tissue.</jats:p>

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