Synovium as a source of interleukin 6 in vitro. Contribution to local and systemic manifestations of arthritis

Synovial inflammation is often associated with systemic changes, such as increased levels of acute phase proteins and hypergammaglobulinemia, which cannot be explained by the cytokines described in synovial fluids and synoviocyte secretions. Interleukin 6 (IL-6) has recently been characterized as a mediator of multiple inflammatory responses. This cytokine promotes T and B lymphocyte growth and differentiation, and acute phase protein synthesis. We therefore examined IL-6 production by human synoviocytes and its presence in synovial fluids. In vitro, synoviocytes spontaneously released IL-6, which was increased by IL-1 and tumor necrosis factor-alpha. Synoviocyte-derived IL-6 activity was able to induce hybridoma-plasmacytoma proliferation, and immunoglobulin and acute-phase protein synthesis. The synovial fluids from patients with diverse arthropathies contained IL-6 activity, but higher levels were present in inflammatory arthropathies than in osteoarthritis. These results demonstrate that synoviocytes are a potent source of IL-6, which can contribute to important manifestations of inflammatory arthropathies.