In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases.
OBJECTIVE
To determine the major source of eicosanoid release in arthritic joint tissues and to examine the modulation of this release by indomethacin and diclofenac.


METHODS
Release of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, leukotriene B4 (LTB4), and LTC4 was measured in supernatants of synovial tissue, cartilage, and bone incubates from patients with osteoarthritis, active rheumatoid arthritis (RA), inactive RA, and pseudogout. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids.


RESULTS
Addition of the divalent cation ionophore A23187 resulted in significant release of all eicosanoids measured from synovial tissue, but not from cartilage, cortical bone, or cancellous bone. PG release was significantly inhibited by the addition of indomethacin or diclofenac at either 10(-5) moles/liter or 10(-7) moles/liter. The amount of LTC4 released from cartilage and bone was only slightly above the detection limit of the RIA, whereas large amounts were released from synovial tissue. Neither indomethacin nor diclofenac had an effect on LTC4 release. LTC4 release from synovial tissue of patients with inactive RA was significantly decreased in comparison with the levels from synovial tissue of patients with the other joint diseases. There was no significant difference in PG release among patients in the various disease groups.


CONCLUSIONS
Synovial tissue appears to be the major source of eicosanoids in synovial fluid. Indomethacin and diclofenac inhibit the release of PG, but not LT, from various joint tissues.
Wittenberg
R H
RH
Department of Orthopaedic Surgery, Ruhr University, Bochum, Germany.
Willburger
R E
RE
Kleemeyer
K S
KS
Peskar
B A
BA
D001168:Arthritis / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism*; D002805:Chondrocalcinosis / Q000378:metabolism; D046508:Culture Techniques; D004008:Diclofenac / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*
D015777:Eicosanoids; D015289:Leukotrienes; D011453:Prostaglandins; D004008:Diclofenac; D007213:Indomethacin