INHIBITION OF NITRIC-OXIDE SYNTHASE (NOS) AGGRAVATES STAPHYLOCOCCUS-AUREUS SEPTICEMIA AND SEPTIC ARTHRITIS

The aim of this study was to assess the role of NO and its metabolites in bacterial arthritis. The murine model of haematogenously acquired septic arthritis was used. Swiss mice treated with NOS inhibitors (N-G -monomethyl-L-arginine or N-omega-nitro-L-arginine methyl ester) were injected intravenously with toxic shock syndrome toxin-1 (TSST-1) prod ucing Staphylococcus aureus LS-1. Arthritis was evaluated clinically a nd histopathologically. Serum cytokine levels, bacterial isolates and intracellular capacity of macrophages to kill bacteria were also analy sed. The frequency of arthritis in mice treated with NOS inhibitors wa s three to four-fold higher than that in non-treated controls (75% ver sus 20%). The severity of arthritis, expressed as mean arthritic index , was 1.4 and 0.4, respectively. Cartilage and/or bone destruction occ urred in 63% of NOS inhibitor-treated mice, but only in 10% of control s. Also, the cumulative septicaemia-induced mortality was clearly high er in mice treated with NOS inhibitors compared with non-treated contr ols. Intracellular killing capacity of the peritoneal macrophages, tre ated in vitro with NOS inhibitors, was decreased. Thus, 24 h after bac terial inoculation peritoneal macrophages pretreated with NOS inhibito rs killed more than 10 times less bacteria than the control ones (P < 0.01). We conclude that NOS inhibitors aggravate S. aureus arthritis, possibly by inducing impairment of the intracellular killing capacity of macrophages.