Modulation of cell recruitment by anti-inflammatory agents in antigen-induced arthritis

Abstract

Methods: Rabbits with antigen-induced arthritis were treated with MXC, DCF, or not treated. After 48 hours, synovial fluid (SF) leucocyte influx and prostaglandin E₂ (PGE₂) 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 PGE₂ concentration, and an increased expression of IL8 and MCP-1. Both non-steroidal anti-inflammatory drugs (NSAIDs) reduced PGE₂ 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.

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Figure 1 .

IL8 (A–D) and MCP-1 (E–H) SM immunostaining (x200). Healthy controls (A, E); untreated group (B, F); MXC treated rabbits (C, G); DCF treated rabbits (D, H). Semiquantitative scoring for IL8 (I) and MCP-1 (J) of the different groups (*p<0.05 v non-treated).

Figure 2 .

IL8 and MCP-1 expression in SM. Representative RT-PCR experiment (A). Densitometry of IL8 (B) and MCP-1 (C) bands corrected by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression.