SUPERANTIGEN CAN REACTIVATE BACTERIAL-CELL WALL-INDUCED ARTHRITIS

Intravenous injection of toxic shock syndrome toxin-1 (TSST-1) produce d by Staphylococcus aureus, can reactivate arthritis in a rat ankle jo int that has been previously inflamed by injection of peptidoglycan-po lysaccharide polymers isolated from the cell walls of group A streptoc occi. The severity and chronicity of this renewed arthritis is dose de pendent and at higher doses (125 mug/kg) a prolonged joint inflammatio n with pannus formation and marginal erosion of cartilage and bone is induced after a single injection of TSST-1. Only modest synovial hyper plasia is induced in control ankle joints by systemic injection of TSS T-1. Another superantigen, streptococcal pyrogenic exotoxin induces a much weaker, acute reactivation of arthritis that resolves by 2 days. Repeated injections of TSST-1 at 7-day intervals give the same undimin ished pattern of joint response, but the joint swelling persists at a higher level with each succeeding injection. Cyclosporin A suppresses all phases of the recurrent arthritis, indicating that TSST-1 could be functioning through its property of a superantigen activating T lymph ocytes. Il-1 receptor antagonist and anti-TNF-alpha neutralizing antib ody, which reduce reactivation of arthritis by peptidoglycan-polysacch aride polymers, have no effect on reactivation by TSST-1. This experim ental model provides a means to examine in vivo the possible role of s uperantigens in rheumatoid arthritis and related diseases, and to anal yze the cellular and molecular pathways induced by this family of micr obial products.