15-Hydroxy-eicosatetraenoic acid (15-HETE) inhibits carrageenan-induced experimental arthritis and reduces synovial fluid leukotriene B4 (LTB4).
15-Hydroxy-eicosatetraenoic acid (15-HETE), a product of arachidonic acid, has no proinflammatory capacity, but can inhibit the formation and the chemotactic response of neutrophils to leukotriene B4 (LTB4), a potent mediator of inflammation. The purpose of the present study was to determine whether intraarticular administration of 15-HETE in carrageenan-induced acute arthritis might decrease the levels of LTB4 in synovial fluid and modify the arthritis. A bilateral acute knee joint arthritis was established in 7 dogs by intraarticular injections of carrageenan every third day. To the right joints, 15-HETE was administered both concomitantly with the carrageenan injections and continuously via an osmotic pump. In samples of synovial fluid obtained on day 0, 3 and 10 PGE2 and LTB4 were determined using reversed phase high performance liquid chromatography combined with radioimmunoassays and neutrophil chemokinesis. In the presence of 15-HETE the clinical severity of arthritis was significantly reduced and the volume of synovial effusate was decreased on an average by 42%. Furthermore, the relative number of neutrophils in histological sections of synovial tissue was decreased by 58%. Intraarticular caragheenan injections induced LTB4 formation, and maximum levels were obtained on day 3 (279.2 +/- 148.2 pg/joint). PGE2 was also present on day 3, but maximum levels were detected on day 10 (9.5 +/- 4.8 ng/joint). In joints injected with both carragheenan and 15-HETE the levels of LTB4 on days 3 and 10 were inhibited by 90% and 83%, respectively. For PGE2 a small but insignificant decrease was found on both day 3 and on day 10. These results show that LTB4 may be an important mediator of acute arthritis induced by carragheenan in dogs, and that intraarticular administration of 15-HETE can modify this arthritis by inhibiting LTB4 formation.
Fogh
K
K
Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.
Hansen
E S
ES
Herlin
T
T
Knudsen
V
V
Henriksen
T B
TB
Ewald
H
H
Bünger
C
C
Kragballe
K
K
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D002351:Carrageenan / Q000037:antagonists & inhibitors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D006893:Hydroxyeicosatetraenoic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects; D011863:Radioimmunoassay; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism*
D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D002351:Carrageenan; D015232:Dinoprostone