EFFECT OF ANIMAL AGE AND CHRONICITY OF INTERLEUKIN-1 EXPOSURE ON CARTILAGE PROTEOGLYCAN DEPLETION IN-VIVO

Rheumatoid arthritis and osteoarthritis are characterized by an early depletion of cartilage proteoglycans, which leads to a decrease in car tilage compressibility and, eventually, to a loss of joint function. I nterleukin-1, which is thought to have a role in mediating this loss o f proteoglycans in arthritis, induces an acute depletion of proteoglyc ans from articular cartilage following intra-articular injection in ra bbits. As the structure and metabolism of proteoglycans are known to c hange with age, my laboratory investigated the effect of age on deplet ion and recovery of proteoglycans in response to interleukin-1 in the rabbit. Loss of cartilage proteoglycans induced by interleukin-1 was l ess severe in immature animals, increased until the age of sexual matu rity, and then remained constant. The rate of recovery and compensator y overshoot in the rate of proteoglycan synthesis following challenge with interleukin-l was more rapid in immature animals and may have bee n responsible for the quicker return of the cartilage proteoglycan con tent to control levels in younger animals. With multiple exposures to interleukin-l at time intervals too short for recovery to occur, small er amounts of interleukin-1 induced loss of proteoglycans, and the pro teoglycan content and the rate of synthesis remained depressed longer after treatment had stopped. The decreased ability of mature cartilage to replace proteoglycans rapidly after exposure to cytokines would in crease the probability of subsequent inflammatory episodes before reco very is complete; this may result in increased susceptibility of adult cartilage to proteoglycan depletion.