Superantigen can reactivate bacterial cell wall-induced arthritis.
Intravenous injection of toxic shock syndrome toxin-1 (TSST-1) produced by Staphylococcus aureus, can reactivate arthritis in a rat ankle joint that has been previously inflamed by injection of peptidoglycanpolysaccharide polymers isolated from the cell walls of group A streptococci. The severity and chronicity of this renewed arthritis is dose dependent and at higher doses (125 micrograms/kg) a prolonged joint inflammation with pannus formation and marginal erosion of cartilage and bone is induced after a single injection of TSST-1. Only modest synovial hyperplasia is induced in control ankle joints by systemic injection of TSST-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 undiminished 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 lymphocytes. II-1 receptor antagonist and anti-TNF-alpha neutralizing antibody, which reduce reactivation of arthritis by peptidoglycan-polysaccharide polymers, have no effect on reactivation by TSST-1. This experimental model provides a means to examine in vivo the possible role of superantigens in rheumatoid arthritis and related diseases, and to analyze the cellular and molecular pathways induced by this family of microbial products.
Schwab
J H
JH
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill 27599.
Brown
R R
RR
Anderle
S K
SK
Schlievert
P M
PM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001170:Arthritis, Infectious / Q000209:etiology* / Q000473:pathology; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D016572:Cyclosporine / Q000494:pharmacology; D004768:Enterotoxins / Q000276:immunology*; D005098:Exotoxins / Q000276:immunology; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D008565:Membrane Proteins; D011135:Polysaccharides, Bacterial / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D012795:Sialoglycoproteins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens; D013601:T-Lymphocytes / Q000502:physiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D053590:Interleukin 1 Receptor Antagonist Protein; D008565:Membrane Proteins; D011135:Polysaccharides, Bacterial; D012795:Sialoglycoproteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C027951:erythrogenic toxin; C036112:streptococcal polysaccharide group A; D016572:Cyclosporine