Effect of indomethacin on swelling, lymphocyte influx, and cartilage proteoglycan depletion in experimental arthritis

Article Abstract:

The non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat various disorders characterized by synovitis, the inflammation of the synovial membrane which lines the joint. Common conditions involving synovitis are gout, osteoarthritis, and rheumatoid arthritis. NSAIDs relieve pain, inflammation, and fever by preventing the production of prostaglandins, fatty acid compounds that are involved in inflammation. However, in addition to relieving the pain from inflammation, NSAIDs may actually worsen the bone destruction associated with joint diseases. NSAIDs have been shown to prevent the production of chondrocyte proteoglycans, which are proteins that contribute to the structure of cartilage tissue, and therefore it appears that NSAIDs cause cartilage degeneration. The effects of the NSAID indomethacin on swelling, production of prostaglandins, cartilage proteoglycan loss, and accumulation of lymphocytes, a type of immune cell, were assessed in rabbits with experimentally induced rheumatoid arthritis (RA). RA is an inflammatory joint disease characterized by stiffness, swelling, enlargement of the cartilage, and pain. Indomethacin decreased joint swelling and the production of prostaglandin E2. But the drug also increased the loss of proteoglycan from joint cartilage and caused the accumulation of lymphocytes. The findings show that although NSAIDs improve inflammation, thereby reducing pain, these drugs may also have significant adverse effects on joint cartilage. (Consumer Summary produced by Reliance Medical Information, Inc.)

Models, Drug therapy, Nonsteroidal anti-inflammatory drugs, Nonsteroidal anti-inflammatory agents, Rheumatoid arthritis, Indomethacin

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Fluid movement across synovium in healthy joints: role of synovial fluid macromolecules

Article Abstract:

Different macromolecules in joint fluid pass through the synovial cell layer at different rates in healthy joints. Synovium refers to the membrane that lines the cavity of joints. Researchers studied the flow of fluid through the synovium of a rabbit knee. The protein albumin is flushed through the synovial fluid at a much faster rate than the substance, hyaluronan. Albumin turnover through synovial fluid of the rabbit knee is one hour, versus a 20-28 hour turnover of hyaluronan in the rabbit shoulder. Hyaluronan may be retained by the synovial lining for its synovium-specific functions. One of its functions may be to prevent the escape of too much synovial fluid through the joint lining, especially during joint exertion. Albumin in joint fluid regulates fluid pressure, while hyaluronan controls viscosity.

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Consensus statement

Article Abstract:

Attendees of a September 1994 conference on synovium discussed issues related to cell biology research on synovium, the membrane that lines joints. Research on synovium relates to rheumatoid disease. Attendees agreed that macrophage cells of the synovium differ from synovial fibroblast cells and are derived from bone marrow. The relative counts of synovial macrophages and fibroblasts in disease states and in health are unknown. Also unknown is how the innermost part of the synovium remains a layer. The ability of the intercellular adhesion molecule-1 to bind hyaluronan may identify synovial function. Synovial macrophages, fibroblasts, and lymphocytes may activate genes related to arthritis. Polymerase chain reaction techniques may identify substances in synovium that cause disease.

Inflammation

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