Sn. Lichtman et al., REACTIVATION OF ARTHRITIS INDUCED BY SMALL-BOWEL BACTERIAL OVERGROWTHIN RATS - ROLE OF CYTOKINES, BACTERIA, AND BACTERIAL POLYMERS, Infection and immunity, 63(6), 1995, pp. 2295-2301
Arthritis is often associated with intestinal diseases, but the etiolo
gy is not known. We developed a rat model whereby arthritis was reacti
vated by experimental small bowel bacterial overgrowth (SBBO). Self-li
mited, monoarticular arthritis was induced by intra-articular injectio
n of 2 mu g of rhamnose peptidoglycan-polysaccharide derived from grou
p A streptococci into the ankle joints in female Lewis rats. Eleven da
ys after intra-articular injection, when swelling was resolving, exper
imental SBBO induced by surgical creation of jejunal self-filling blin
d loops reactivated arthritis, but SBBO induced by creation of self-em
ptying blind loops, which minimally increases luminal bacteria, and sh
am operation did not (P < 0.001). Increased joint diameters in rats wi
th self-filling blind loops persisted for at least 56 days after surge
ry. 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 se
condary to intestinal injury. Recombinant bactericidal/permeability-in
creasing protein, an agent which neutralizes endotoxin, and metronidaz
ole, which is active against anaerobic bacteria, prevented arthritis (
P < 0.001), but polymyxin B (which also neutralizes endotoxin) and gen
tamicin had no effect. Mutanolysin, an enzyme which degrades peptidogl
ycan-polysaccharide from group A streptococci, exacerbated arthritis f
or the first 6 days but then diminished joint swelling from 12 to 21 d
ays after surgery (P < 0.001). These studies introduce a reproducible
animal model of reactivation of arthritis secondary to intestinal inju
ry and demonstrate a role for bacterial products from endogenous enter
ic organisms.