The Role of Prostaglandins in Rabbit Monoarticular Arthritis

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 Mg/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.

Excitation and sensitization of fine articular afferents from cat's knee joint by prostaglandin E2.

“…As such an -experimental inflammation is promoted by endogenous inflammatory mediators including PGE2 (Willis, 1969;DiRosa et al 1971;Blackham et al 1974;Moncada et al 1975;Higgs & Salmon, 1979;Holsapple et al 1980;Higgs & Moncada, 1983) it may be assumed that these mediators also contribute to the sensitization of group III and IV units from inflamed joints. The present data show that PGE2 is able to induce a long-lasting increase of sensitivity to movements in group III units including some of those having a high threshold to movements in the control period.…”

Role of prostaglandins in regulation of blood flow and modulation of sympathetic vasoconstriction in normal and acutely inflamed rabbit knee joints

“…Neural influences are known to be important, since it has been shown that electrical stimulation of sympathetic postganglionic fibres innervating the knee joint potently constricts articular blood vessels in the dog (Cobbold & Lewis, 1956), cat ) and rabbit (Ferrell & Najafipour, 1992), and that these exhibit vasoconstrictor 'tone' even in deeply anaesthetized animals (Cobbold & Lewis, 1956;. It has been shown that blood vessels in different species have the capacity to synthesize prostaglandins (Tuvemo & Wide, 1973;Aiken, 1974;Terragno, Crowshaw, Terragno & McGiff, 1975) and these agents change the vascular resistance (Blumberg, Denny, Marshall & Needleman, 1977) and modulate Although it is known that the synovial fluid from inflamed joints contains a high level of PGs (Blackham, Farmer, Radziwonik & Westwick, 1974; O'Byrne, Blancuzzi, Wilson, Wong, Peppard, Simke & Jeng, 1990), the role of these agents in regulation of blood flow and sympathetic vasoconstriction in normal and inflamed joints is unknown.…”

Studies on the Relative Effects of Prostaglandins, Bradykinin, 5‐hydroxytryptamine and Histamine on the Synovial Microcirculation in Dogs

“…Prostaglandin E2 was also a potent vasodilator, approximately 5-10 times less potent than prostaglandin El. These results are of interest in that prostaglandin El is reported to be the main prostaglandin in the synovial fluid of inflamed joints both in experimental animals (Blackham et al, 1974) and in rheumatoid arthritis (Higgs et al, 1974).…”