RELATIONS BETWEEN FUNCTIONAL, INFLAMMATORY, AND DEGENERATIVE PARAMETERS DURING ADJUVANT ARTHRITIS IN RATS

We assessed the time-course of adjuvant arthritis (AA) in Lewis rats, using biotelemetry to monitor the rat's spontaneous locomotor activity and body temperature, and studied the evolution of the arthritic inde x, circulating concentrations of inflammation-promoting cytokines, car tilage proteoglycan synthesis, and the effect of indomethacin as a cyc looxygenase inhibitor to evaluate prostaglandin (PG) contribution in A A. The injection of complete Freund's adjuvant on clay 0 (D0) induced a marked, transient loss of locomotor activity (D1-D4; initial phase) and then a second phase of hypomobility peaking on D15 and thereafter irreversible (D16-D20; arthritic phase). Fever peaked first on D1 and again between D13 and D17. The primary hyperthermia was associated wit h increases in plasma interleukin-6 and tumor necrosis factor-alpha co ncentrations and seemed to be partly PG dependent. Proteoglycan synthe sis inhibition in the patellar cartilage increased gradually, spreadin g from the injected paw to the contralateral paw. It was corrected on D20 by preventive and curative indomethacin treatments. Indomethacin a lso greatly relieved hypomobility during the systemic phase of AA (D10 -D15). The combination of information about cartilage metabolism, body temperature, locomotor activity, and cytokine in this study permits a nalysis of analgesic, antipyretic, anti-inflammatory, and chondroprote ctive properties of drugs in the various phases of AA. Thus, using a n ew methodology, we have discriminated the different phases of the dise ase and confirmed the symptomatic and systemic inhibitory effect of in domethacin on fever, activity, and cartilage metabolism.