GS inhibits the synthesis of proinflammatory mediators in HOC stimulated with IL-1beta through a NFkappaB-dependent mechanism. Our study further supports the role of GS as a symptom- and structure-modifying drug in the treatment of OA.

Background: Besides its proinflammatory properties, prostaglandin E 2 (PGE 2 ) acts as a regulator of the expression of inducible genes. Inhibition of PGE 2 synthesis might thus result in a paradoxical deleterious effect on inflammation. Objective: To examine the effect of PGE 2 on monocyte chemoattractant protein-1 (MCP-1) expression in cultured synovial fibroblasts (SF) stimulated with interleukin (IL)1b. Methods: MCP-1 expression was assessed in SF stimulated with IL1b in the presence of PGE 2 or different NSAIDs by RT-PCR or northern blot and immunocytochemistry. Expression of cyclo-oxygenase (COX) isoforms was studied by western blot techniques. The role of PGE 2 receptors (EP) in PGE 2 action was assessed employing EP receptor subtype-specific agonists. Results: PGE 2 significantly inhibited IL1b induced MCP-1 expression in SF in a dose dependent manner. IL1b increased COX-2 and did not alter COX-1 synthesis in SF. 11-Deoxy-PGE 1 , an EP 2 /EP 4 agonist, reproduced PGE 2 action on MCP-1 expression. Butaprost, a selective EP 2 agonist, was less potent than PGE 2 . Sulprostone, an EP 1 /EP 3 agonist, had no effect on IL1b induced MCP-1 expression. Inhibition of endogenous PGE 2 synthesis by NSAIDs further enhanced MCP-1 mRNA expression in IL1b stimulated SF, an effect prevented by addition of exogenous PGE 2 . Conclusion: Activation of EP 2 /EP 4 receptors down regulates the expression of MCP-1 in IL1b stimulated SF, while PGE 2 pharmacological inhibition cuts off this signalling pathway and results in a superinduction of MCP-1 expression. The data suggest that NSAIDs may intercept a natural regulatory circuit controlling the magnitude of inflammation, which questions their continuous administration in inflammatory joint diseases.

Objective: To study the effect of meloxicam (MXC) and diclofenac (DCF) on the recruitment of leucocytes during acute experimental arthritis. Methods: Rabbits with antigen-induced arthritis were treated with MXC, DCF, or not treated. After 48 hours, synovial fluid (SF) leucocyte influx and prostaglandin E 2 (PGE 2 ) levels were evaluated. Interleukin 8 (IL8) and monocyte chemotactic peptide-1 (MCP-1) expression and synthesis were studied in the inflamed tissues. Results: Arthritic knees showed synovial effusion with a high leucocyte count and PGE 2 concentration, and an increased expression of IL8 and MCP-1. Both non-steroidal anti-inflammatory drugs (NSAIDs) reduced PGE 2 levels and the polymorphonuclear cell (PMN) concentration in SF, while the mononuclear cell (MN) concentration was unchanged in the treated groups in comparison with controls. A definite reduction of IL8 levels was obtained with the treatments, but the drugs did not prevent the up regulation of MCP-1. Conclusion: The effect of these NSAIDs in acute arthritis may be related to the down regulation of IL8 production. The results suggest a differential effect of anti-inflammatory drugs on PMN and MN recruitment to the joint.

Comparison of the features of arthroscopic synovial biopsies with biopsy samples obtained at surgery

The present study was undertaken to investigate, if the non-steroidal anti-inflammatory drug (NSAID) piroxicam (CAS 36322-90-4) Fast-Dissolving Dosage Form (FDDF) can be absorbed in the oral mucosa. Piroxicam FDDF was administrated under the tongue to rats with an oesophagus ligation (OL) to prevent the drug entering the stomach and in turn its absorption by the classic way. A group of sham-operated (SO) animals received the same piroxicam FDDF dose. After drug administration, a pharmacokinetic study with serial serum sample extractions at 0, 15, 30, 60 and 120 min was performed. It has been found a prompt increase in serum piroxicam levels in OL-rats, which showed different pharmacokinetics from SO-rats. Areas under curve (AUCs) of OL-rat serum piroxicam levels were higher at 15, 30 and 60 min compared to SO-animals. These results indicate that piroxicam FDDF is absorbed in the rat oral mucosa. Moreover, during the first hour, drug absorption by oral mucosa rendered higher piroxicam levels than gastric absorption.