Nitric oxide synthase inhibitor influences prostaglandin and interleukin-1 production in experimental arthritic joints

Abstract.

Objective: To assess involvement of nitric oxide (NO) in the increase in eicosanoid and interleukin- 1 (IL-1) levels in the synovial fluid during antigen-induced arthritis (AIA) in rabbits treated with a competitive inhibitor of NO synthesis. ¶Subjects: Thirteen New Zealand White rabbits were sensitized with 5 mg of methylated bovine serum albumin (mBSA). Arthritis was induced in the knee joint by injecting 0.5 ml of a sterile solution of mBSA (2 mg/ml) into the intra-articular cavity. ¶Treatment: Prior to the induction of arthritis, the animals received N-Omega-Nitro-L-Arginine Methyl Ester (LNAME) or N-Omega-Nitro-D-Arginine Methyl Ester (DNAME) for 2 weeks, both at a dose of 20 mg/kg/day mixed with drinking water. ¶Methods: Leukocyte efflux (total and differential white cell count), vascular permeability (Evans's blue method), synovial PMN cell infiltrate, and total nitrite (NO₂.)/nitrate (NO₃.) (HPLC), PGE₂, TxB₂, LTB₄ (radioimmunoassay), and IL-1<beta> (ELISA) levels were quantified in the synovial fluid. ¶Results: LNAME but not DNAME significantly suppressed leukocyte efflux and protein leakage into the articular cavity as well as synovial PMN cell infiltrate. Total NO₂./NO₃., PGE₂ and IL-1<beta> levels were significantly reduced in the synovial fluid of LNAME treated animals. TxB₂ and LTB₄ were not affected by LNAME treatment. ¶Conclusion: These data clearly show NO involvement in the IL-1-induced PGE₂ production in the synovial fluid of antigen- induced arthritis in rabbits.