Effects of anti-inflammatory drugs on lipopolysaccharide-challenged and -unchallenged equine synovial explants.
OBJECTIVE
To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics.


METHODS
Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses.


METHODS
Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine (FNX), ketoprofen (KET), carprofen (CRP), meloxicam (MEL), low-concentration methylprednisolone (METH), high-concentration METH, dimethyl sulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Following 48 hours of culture, medium was assayed for PGE2 and hyaluronan concentration. Synovial explants were assessed for viability and histomorphologic characteristics.


RESULTS
For the LPS-challenged explants, PBZ, FNX, KTP CRF MEL, and low-concentration METH suppressed PGE2 production, compared with LPS challenge alone. Only MEL suppressed PGE2 production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% viability and there was no significant difference in viability or hyaluronan production among explants. Histomorphologic scores were significantly decreased for explants treated with low-concentration METH or DMSO.


CONCLUSIONS
PBZ, FNX, KTP, CRFP MEL, and low-concentration METH suppressed PGE2 production in LPS-challenged explants. Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphologic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used nonsteroidal anti-inflammatory drugs suppress induced synovial membrane PGE2 production without detrimental effects on synovial membrane viability and function.
Moses
V S
VS
The College of Veterinary Medicine, The Ohio State University, Columbus 43210, USA.
Hardy
J
J
Bertone
A L
AL
Weisbrode
S E
SE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D003002:Clonixin / Q000031:analogs & derivatives / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D006736:Horses; D006820:Hyaluronic Acid / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007660:Ketoprofen / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D000077239:Meloxicam; D008775:Methylprednisolone / Q000494:pharmacology; D009924:Organ Culture Techniques; D010653:Phenylbutazone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D002227:Carbazoles; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D013843:Thiazines; D013844:Thiazoles; C014558:flunixin meglumine; D006820:Hyaluronic Acid; D007660:Ketoprofen; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C007005:carprofen; D010653:Phenylbutazone; D015232:Dinoprostone; D003002:Clonixin; D000077239:Meloxicam; D008775:Methylprednisolone