Localization of Tumor Necrosis Factor α in Synovial Tissues and at the Cartilage–Pannus Junction in Patients With Rheumatoid Arthritis

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Abstract
Using immunoaffinity‐purified polyclonal anti‐human recombinant tumor necrosis factor α (TNFα) F(ab′)2 fragments and immunohistochemical techniques, the cells that make TNFα were localized in the inflamed synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Anti‐TNFα antibody–stained cells were demonstrated in 9 of 11 RA and 2 of 4 OA but none of 5 normal synovial membranes examined. In RA, 26–64% of the lining layer cells were positive for TNFα. In the interaggregate area, 10–30% of the cells contained TNFα, often in a perivascular distribution, and up to 19% of the cells in lymphoid aggregates stained for TNFα. Some endothelial cells also stained with these antibodies. In OA tissues, the TNFα‐containing cells were found predominantly in the deeper layer. Cells containing TNFα were also found at the cartilage–pannus junction in all 4 RA specimens examined. Double immunofluorescence analysis demonstrated that most TNFα‐secreting cells in the RA synovial membrane expressed the monocyte/macrophage marker antigens CD11b and CD14, and a few expressed the T cell marker CD3. Our findings provide histologic evidence that TNFα is locally produced in the lining and deeper layers of the synovium by cells of the mónocyte/macrophage lineage, supporting its role in inflammation. Further, our findings demonstrate that TNFα is produced by cells at the cartilage–pannus junction, which could affect chondrocyte metabolism, leading to the cartilage degradation in RA.