Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: Implications for the role of cytokines in cartilage destruction and repair

Cytokine release at the cartilage/pannus junction (CPJ) may be involved in cartilage destruction and tissue repair in rheumatoid arthritis (RA). Tissue samples of CPJ from 12 RA patients were examined for the presence of cytokines using immunohistochemical techniques with immunoaffinity purified F(ab′)₂ antibodies raised against recombinant human cytokines. Twenty-four areas of distinct CPJ at which a discrete junction between cartilage and overlying pannus exists were observed. In all specimens, tumour necrosis factor (TNF)-α, interleukin (IL)-1α. IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-β1 were detected in cells in pannus particularly along the surface of cartilage and at the site of cartilage erosion. Double immunofluorescence staining showed that most cytokine containing cells also labelled with a macrophage marker (CD68). About 50% of blood vessel endothelial cells stained for GM-CSF. Twelve areas of diffuse fibroblastic CPJ, at which an indistinct margin is seen between cartilage and pannus were examined. At this site, TGF-β1 was the only cytokine detected in fibroblast-like cells. None of these cytokines were detected in synovial tissue at the normal synovium/cartilage junction. Chondrocytes from all 11 normal specimens as well as those from RA patients stained for IL-1α, TNF-α, IL-6, GM-CSF and TGF-β1, especially those close to subchondral bone. However, IL-1β, interferon-γ and lymphotoxin were not detected in either the normal synovium/cartilage junction or rheumatoid CPJ. These results suggest that cytokines are produced by normal chondrocytes and may therefore be involved in normal cartilage homeostasis, but in RA patients the additional production of IL-1, TNF-α, IL-6 and GM-CSF at the distinct CPJ may be involved in immune and inflammatory responses and induce cartilage destruction. The demonstration of TGF-β1 at both distinct and diffuse fibroblastic CPJ suggests that this cytokine may be involved in tissue repair.