Animal models of intestinal and joint inflammation.
Recent rodent models have been exploited to explore mechanisms of intestinal and joint inflammation. HLA-B27 transgenic rats develop colitis, gastritis, and arthritis when raised in a conventional environment, but have no evidence of inflammation under germfree (sterile) conditions. Metronidazole treatment attenuates gastrointestinal inflammation, suggesting that anaerobic bacteria are important. Experimental bacterial over-growth of predominantly anaerobic bacteria reactivates arthritis in Lewis rats which have been previously injected intra-articularly with bacterial cell wall polymers. Reactivation arthritis is mediated by interleukin-1, tumour necrosis factor-alpha, and can be blocked by metronidazole. Intramural injection of the bacterial cell wall polymer, peptidoglycan-polysaccharide, leads to biphasic, chronic granulomatous enterocolitis and peripheral arthritis in Lewis rats, but only transient intestinal inflammation and no arthritis in Buffalo or MHC-matched Fischer rats. Chronic granulomatous inflammation is mediated by T lymphocytes and interleukin-1 and is dependent on persistent antigenic stimulation by poorly biodegradable bacterial polymers. Results in these models firmly incriminate resident normal enteric flora (especially anaerobes), bacterial products, and host genetic susceptibility in the pathogenesis of spondyloarthropathies. We suggest that increased uptake of luminal bacterial components across the inflamed mucosa leads to systemic distribution of these arthropathic products. The genetically susceptible host develops reactive arthritis due to defective downregulation of inflammation in response to immunologically active bacterial components.
Sartor
R B
RB
Department of Digestive Diseases, University of North Carolina at Chapel Hill 27599-7080, USA.
Rath
H C
HC
Lichtman
S N
SN
van Tol
E A
EA
D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology*; D003092:Colitis / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology