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

This research evaluated the impact of various anti-inflammatory drugs on lipopolysaccharide-challenged and unchallenged horse synovial membranes in terms of prostaglandin E2 (PGE2) and hyaluronan production, as well as viability and histological characteristics. The study found that many commonly used drugs suppress induced synovial membrane PGE2 production without harming the membrane’s function and viability.

Methodology

• Synovial membranes were collected from three types of joints (carpal, tarsocrural, and femoropatellar) in six adult horses.
• The membranes from each horse were processed into small pieces, pooled together, and treated with either no drug (for control purposes), a specific anti-inflammatory drug, lipopolysaccharide (LPS) alone, or a combination of LPS and an anti-inflammatory drug.
• The anti-inflammatory drugs used were phenylbutazone, flunixin meglumine, ketoprofen, carprofen, meloxicam, and different concentrations of methylprednisolone and a COX-2 inhibitor (combined with DMSO).
• Following 48 hours of culture, the medium in which they were grown was tested for PGE2 and hyaluronan concentrations. The explants were also analysed for viability and histomorphologic characteristics.

Results

• For the LPS-challenged explants, phenylbutazone, flunixin meglumine, ketoprofen, carprofen, meloxicam, and the low concentration of methylprednisolone, suppressed PGE2 production compared with the LPS-challenged controls.
• Only meloxicam was found to suppress PGE2 production from LPS-challenged explants when compared with unchallenged explants.
• The synovial explants maintained over 90% viability regardless of treatment type, and no significant difference was observed in hyaluronan production amongst the different explants.
• Histomorphologic scores, a measure of tissue structure and composition, were significantly decreased for explants treated with low concentration of methylprednisolone or dimethyl sulfoxide.

Conclusion

• The study concludes that phenylbutazone, flunixin meglumine, ketoprofen, carprofen, meloxicam, and low concentration of methylprednisolone, were successful in suppressing PGE2 production in LPS-challenged explants. Meloxicam showed more selective suppression of COX-2 activity.
• Histomorphologic scores suggested potential detrimental effects of low-concentration methylprednisolone, dimethyl sulfoxide, and the experimental COX-2 inhibitor.
• Importantly, it was shown that commonly used nonsteroidal anti-inflammatory drugs can suppress synovial membrane PGE2 production without causing detrimental effects on the membrane’s functioning and viability.