Reactivation of arthritis induced by small bowel bacterial overgrowth in rats: role of cytokines, bacteria, and bacterial polymers.
Arthritis is often associated with intestinal diseases, but the etiology is not known. We developed a rat model whereby arthritis was reactivated by experimental small bowel bacterial overgrowth (SBBO). Self-limited monoarticular arthritis was induced by intra-articular injection of 2 micrograms of rhamnose peptidoglycan-polysaccharide derived from group A streptococci into the ankle joints in female Lewis rats. Eleven days after intra-articular injection, when swelling was resolving, experimental SBBO induced by surgical creation of jejunal self-filling blind loops reactivated arthritis, but SBBO induced by creation of self-emptying blind loops, which minimally increases luminal bacteria, and sham operation did not (P < 0.001). Increased joint diameters in rats with self-filling blind loops persisted for at least 56 days after surgery. Reactivation of arthritis due to SBBO was prevented by anti-tumor necrosis factor alpha antiserum and interleukin 1 receptor antagonist (P < 0.001), indicating that these cytokines mediate joint swelling secondary to intestinal injury. Recombinant bactericidal/permeability-increasing protein, an agent which neutralizes endotoxin, and metronidazole, which is active against anaerobic bacteria, prevented arthritis (P < 0.001), but polymyxin B (which also neutralizes endotoxin) and gentamicin had no effect. Mutanolysin, an enzyme which degrades peptidoglycan-polysaccharide from group A streptococci, exacerbated arthritis for the first 6 days but then diminished joint swelling from 12 to 21 days after surgery (P < 0.001). These studies introduce a reproducible animal model of reactivation of arthritis secondary to intestinal injury and demonstrate a role for bacterial products from endogenous enteric organisms.
Lichtman
S N
SN
Department of Pediatrics, University of North Carolina at Chapel Hill 27599, USA.
Wang
J
J
Sartor
R B
RB
Zhang
C
C
Bender
D
D
Dalldorf
F G
FG
Schwab
J H
JH
D000818:Animals; D000843:Ankle Joint / Q000473:pathology; D016918:Arthritis, Reactive / Q000209:etiology* / Q000473:pathology; D016207:Cytokines / Q000502:physiology*; D005260:Female; D007421:Intestine, Small / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008795:Metronidazole / Q000494:pharmacology; D010457:Peptidoglycan / Q000633:toxicity*; D011135:Polysaccharides, Bacterial / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D015430:Weight Gain
D016207:Cytokines; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D008795:Metronidazole