THE ROLE OF PROSTAGLANDINS IN RABBIT MONOARTICULAR ARTHRITIS

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Abstract
1 Old English (OE) rabbits produced more severe monoarticular arthritis (MAA) after sensitization and intra-articular challenge with ovalbumin than did either New Zealand White (NZW) or Dutch rabbits. NZW rabbits were better responders than Dutch rabbits. 2 The swelling of the joint in all three strains of rabbits was triphasic. There was an initial acute swelling which appeared to peak at 2–4 days after challenge. This was followed by a decrease in joint size, and then a secondary increase in size beginning 1–2 weeks after challenge. 3 An investigation of MAA in OE rabbits showed that there was an increase in E-type prostaglandins, total leucocyte counts and free acid phosphatase activity in the synovial fluid of the challenged joints at 6 h, 19 h, 47 h, 7 days and 46 days following challenge. There were also histopathological changes at these times. In addition, there was an increase in the surface temperature of both the challenged and non-challenged knees, and a rise in the body temperature. 4 Prostaglandin levels peaked at 19 h and were equivalent to 19 ng E2 per joint. In a separate experiment, the prostaglandin present at 18 h was shown to be mainly E1. Maximum levels of prostaglandin appeared to coincide with maximum joint temperature, but preceded maximum joint swelling and a significant rise in both the number of inflammatory cells and the free acid phosphatase activity in the synovial fluid, all of which occurred at 47 hours. 5 Indomethacin, 7.5 mg/kg orally twice daily, almost completely inhibited the increase in prostaglandin levels in the challenged joints and produced a moderate reduction in joint swelling. It also reduced the increased surface temperature of both knee joints and the raised body temperature. However, indomethacin had no effect on the number of leucocytes present, the free acid phosphatase levels, or the histopathological changes in the joint. 6 The mean plasma level of indomethacin ranged from 0.5 to 3 μg/ml at the time when the animals were killed. 7 Lysosomal enzymes may be more important than prostaglandins in rabbit MAA, and the lack of effect of indomethacin on joint histopathology may be due to its inability to prevent the release of these enzymes.