Induction by chronic autoimmune arthritis in DBA/1 mice by oral administration of type II collagen and Escherichia coli lipopolysaccharide.
We have developed a new model of autoimmune arthritis in DBA/1 mice by feeding chick type II collagen (CII) for 2-3 week intervals over a 15 week period. Clinically evident arthritis occurred in 8/10 mice receiving native CII (nCII; 100 micrograms/mouse) alone at 9-13 weeks. Arthritis was aggravated by the further ingestion of CII, while remission occurred after withdrawal of the CII. Heat-denatured CII (dCII; 200 micrograms/mouse) was also arthritogenic if co-administered with ovoinhibitor (OVI; 2 mg/mouse), a proteinase inhibitor. Co-oral administration of lipopolysaccharide (LPS; 10 micrograms/mouse) with CII enhanced the antibody production and T-cell responses to CII, and induced a more chronic arthritis that progressed spontaneously without further administration of CII or LPS. Long-term oral administration of LPS alone also induced a mild arthritis characterized by destruction of bone rather than cartilage. These observations suggest that abnormal gastrointestinal absorption of dietary mimic antigens and intestinal bacterial toxins can potentially disrupt self-tolerance mechanisms, thereby precipitating or exacerbating autoimmune disease in genetically susceptible individuals.
Terato
K
K
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, 84132, USA.
Ye
X J
XJ
Miyahara
H
H
Cremer
M A
MA
Griffiths
M M
MM
D000284:Administration, Oral; D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000473:pathology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000473:pathology; D002908:Chronic Disease; D003094:Collagen / Q000276:immunology; D003429:Cross Reactions; D004926:Escherichia coli / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
D008070:Lipopolysaccharides; D003094:Collagen