This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lichtman, S. N. Articles by Schwab, J. H. Search for Related Content PubMed PubMed Citation Articles by Lichtman, S. N. Articles by Schwab, J. H.

 Previous Article  |  Next Article 

Infect. Immun., 06 1995, 2295-2301, Vol 63, No. 6
Copyright © 1995, American Society for Microbiology

Reactivation of arthritis induced by small bowel bacterial overgrowth in rats: role of cytokines, bacteria, and bacterial polymers

SN Lichtman, J Wang, RB Sartor, C Zhang, D Bender, FG Dalldorf and JH Schwab
Department of Pediatrics, University of North Carolina at Chapel Hill 27599, USA.

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.

This article has been cited by other articles:

• Hendrickson, B. A., Gokhale, R., Cho, J. H. (2002). Clinical Aspects and Pathophysiology of Inflammatory Bowel Disease. Clin. Microbiol. Rev. 15: 79-94 [Abstract] [Full Text]  
• Rath, H. C., Schultz, M., Freitag, R., Dieleman, L. A., Li, F., Linde, H.-J., Scholmerich, J., Sartor, R. B. (2001). Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice. Infect. Immun. 69: 2277-2285 [Abstract] [Full Text]  
• Schultz, H., Weiss, J., Carroll, S. F., Gross, W. L. (2001). The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies. J. Leukoc. Biol. 69: 505-512 [Abstract] [Full Text]  
• Rath, H. C., Wilson, K. H., Sartor, R. B. (1999). Differential Induction of Colitis and Gastritis in HLA-B27 Transgenic Rats Selectively Colonized with Bacteroides vulgatus or Escherichia coli. Infect. Immun. 67: 2969-2974 [Abstract] [Full Text]  
• Constantinescu, C. S., Wysocka, M., Hilliard, B., Ventura, E. S., Lavi, E., Trinchieri, G., Rostami, A. (1998). Antibodies Against IL-12 Prevent Superantigen-Induced and Spontaneous Relapses of Experimental Autoimmune Encephalomyelitis. J. Immunol. 161: 5097-5104 [Abstract] [Full Text]