| 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. |
| Authors | K Fogh, E S Hansen, T Herlin, V Knudsen, T B Henriksen, H Ewald, C Bünger, K Kragballe
(Affiliation: Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.)
|
| Journal | Prostaglandins
(Prostaglandins)
Vol. 37
Issue 2
Pg. 213-28
(Feb 1989)
ISSN: 0090-6980 UNITED STATES |
| PMID | 2543035
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Hydroxyeicosatetraenoic Acids
- Dinoprostone
- Leukotriene B4
- 15-hydroxy-5,8,11,13-eicosatetraenoic acid
- Carrageenan
|
| Topics |
- Animals
- Arthritis
(chemically induced, metabolism, prevention & control)
- Carrageenan
(antagonists & inhibitors)
- Chemotaxis, Leukocyte
(drug effects)
- Chromatography, High Pressure Liquid
(methods)
- Dinoprostone
(metabolism)
- Dogs
- Hydroxyeicosatetraenoic Acids
(chemical synthesis, pharmacology)
- Leukotriene B4
(metabolism)
- Neutrophils
(drug effects)
- Radioimmunoassay
- Synovial Fluid
(drug effects, metabolism)
|
