Effects of anti-inflammatory drugs on lipopolysaccharide-challenged and -unchallenged equine synovial explants

Objective-To evaluate the effects of anti-inflammatory drugs on lipopolysac charide (LPS)-challenged and -unchallenged equine synovial membrane in term s of production of prostaglandin E-2 (PGE(2)) and hyaluronan, viability, an d histomorphologic characteristics. Sample Population-Synovial membranes were collected from the carpal, tarsoc rural, and femoropatellar joints of 6 adult horses. Procedure-Synovial membranes from each horse were minced and pooled and exp lants 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-c oncentration methylprednisolone (METH), high-concentration METH, dimethyl s ulfoxide (DMSO), or an experimental COX-2 inhibitor (dissolved in DMSO). Fo llowing 48 hours of culture, medium was assayed for PGE(2) and hyaluronan c oncentration. Synovial explants were assessed for viability and histomorpho logic characteristics. Results-For the LPS-challenged explants, PBZ, FNX, KTP: CRP MEL, and low-co ncentration METH suppressed PGE(2) production, compared with LPS challenge alone. Only MEL suppressed PGE(2) production from LPS-challenged explants, compared with unchallenged explants. Synovial explants maintained > 90% via bility and there was no significant difference in viability or hyaluronan p roduction among explants. Histomorphologic scores were significantly decrea sed for explants treated with low-concentration METH or DMSO. Conclusions and Clinical Relevance-PBZ, FNX, KTP CRP MEL, and low-concentra tion METH suppressed PGE2 production in LPS-challenged explants, Meloxicam appeared to have more selective suppression of COX-2 activity. Histomorphol ogic scores suggest detrimental effects of METH, DMSO, and the experimental COX-2 inhibitor. Commonly used non-steroidal anti-inflammatory drugs suppr ess induced synovial membrane PGE2 production without detrimental effects o n synovial membrane viability and function.