Interleukin-1 in Arthritis

The hypothesis is reviewed that interleukin-1 (IL-1) may contribute to the pathology of rheumatoid arthritis. IL-1 is a protein mediator secreted by cells of the macrophage lineage among others. Although the activity of IL-1 is shared by a variety of proteins with different molecular weights and isoelectric points, it is likely that the various biochemical species are all products of a single gene. IL-1 is predominantly recognised for the role it plays in the body’s defence against infection as a stimulant of immune response, neutrophil activation, acute phase changes, and fever. Recently, however, it has become clear that in vitro IL-1 can also modulate the activity of many of the mesenchymal cells which contribute to the architecture of the articular joint. If these activities were expressed in vivo, they could be responsible for several of the characteristic pathological features of rheumatoid arthritis including the synovial hypertrophy, the high hyaluronate and protease content of the synovial fluid, cartilage destruction, and bone resorption. In fact, it has been possible to recover and identify IL-1 in the synovial fluids of arthritic patients. Although a portion of this IL-1 may be derived from the infiltrating leukocytes, the synovium itself is also capable of releasing large amounts of IL-1. From these results, a model of arthritic disease can be constructed in which IL-1 is hypothesised to play a major role in the maintenance of the chronicity and in the eventual joint destruction.