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

Valentine S. Moses The college of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
Centennial Valley Equine Hospital, 2097 S. 104th St., Broomfield, CO 80020.

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 DVM, MS
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Joanne Hardy The college of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Alicia L. Bertone The college of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Steven E. Weisbrode The college of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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 VMD, PhD

Abstract

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.

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

Procedure—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), highconcentration 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, CRP, 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 and Clinical Relevance—PBZ, FNX, KTP, CRP, 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. ( Am J Vet Res 2001;62:54–60)

Abstract

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.

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

Procedure—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), highconcentration 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, CRP, 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 and Clinical Relevance—PBZ, FNX, KTP, CRP, 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. ( Am J Vet Res 2001;62:54–60)

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