Exacerbation of arthritis by IL-1 in rat joints previously injured by peptidoglycan-polysaccharide.
The arthropathic activity of mouse recombinant IL-1 (mrIL-1) after intraarticular (i.a.) injection into rat ankles was investigated. Nanogram quantities of either mrIL-1 alpha or mrIL-1 beta induced an acute transient arthritis. Arthritis induced by i.a. mrIL-1 developed more rapidly and was more severe in ankles previously injured by i.a. injection of group A streptococcal peptidoglycan-polysaccharide (PG-APS) fragments. In addition, a protracted pain response, as judged by severe limping, occurred 60 to 90 min after mrIL-1 injection into joints previously injured by PG-APS or 4 to 6 h after mrIL-1 injection into naive joints. The severity of arthritis was related to the mrIL-1 dose. Arthropathic activity of mrIL-1 alpha was neutralized by goat anti-mouse IL-1 alpha IgG, and the activity of both the alpha and beta preparations was heat labile. Repeated episodes of acute inflammation were induced by repeated i.a. injection of mrIL-1. In naive ankles this led to chronic synovitis without histologic evidence of erosions. However, in joints previously injured by PG-APS, repeated mrIL-1 injection induced a more severe chronic synovitis with a 50% incidence of early pannus formation and limited marginal erosions of cartilage and subchondral bone. Thus, mrIL-1 induces an acute exacerbation of arthritis in joints previously injured by PG-APS and repeated exposure of these joints to mrIL-1 promotes chronic erosive synovitis. These studies provide evidence for an in vivo function of IL-1 and are consistent with its role as one of the mediators in the local regulation of inflammation in recurrences of arthritis induced by bacterial cell wall polymers.
Stimpson
S A
SA
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill 27599.
Dalldorf
F G
FG
Otterness
I G
IG
Schwab
J H
JH
D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007375:Interleukin-1 / Q000494:pharmacology*; D010457:Peptidoglycan / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013297:Streptococcus pyogenes; D013585:Synovitis / Q000150:complications
D007375:Interleukin-1; D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins