15-Hydroxy-eicosatetraenoic acid (15-HETE) inhibits carrageenan-induced experimental arthritis and reduces synovial fluid leukotriene B4 (LTB4)

Prostaglandins. 1989 Feb;37(2):213-28. doi: 10.1016/0090-6980(89)90058-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / chemically induced
  • Arthritis / metabolism
  • Arthritis / prevention & control*
  • Carrageenan / antagonists & inhibitors
  • Chemotaxis, Leukocyte / drug effects
  • Chromatography, High Pressure Liquid / methods
  • Dinoprostone / metabolism
  • Dogs
  • Hydroxyeicosatetraenoic Acids / chemical synthesis
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • Leukotriene B4 / metabolism*
  • Neutrophils / drug effects
  • Radioimmunoassay
  • Synovial Fluid / drug effects
  • Synovial Fluid / metabolism*

Substances

  • Hydroxyeicosatetraenoic Acids
  • Leukotriene B4
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • Carrageenan
  • Dinoprostone