REACTIVATION OF ARTHRITIS INDUCED BY SMALL-BOWEL BACTERIAL OVERGROWTHIN RATS - ROLE OF CYTOKINES, BACTERIA, AND BACTERIAL POLYMERS

Citation
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
Citations number
42
Categorie Soggetti
Immunology,"Infectious Diseases
Journal title
ISSN journal
00199567
Volume
63
Issue
6
Year of publication
1995
Pages
2295 - 2301
Database
ISI
SICI code
0019-9567(1995)63:6<2295:ROAIBS>2.0.ZU;2-W
Abstract
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.