© 1996 British Society for Rheumatology
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INDUCTION OF CHRONIC AUTOIMMUNE ARTHRITIS IN DBA/1 MICE BY ORAL ADMINISTRATION OF TYPE II COLLAGEN AND ESCHERICHIA COLl LIPOPOLYSACCHARIDE
Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine 50 North Medical Drive and the Research Service of the Veteran's Affairs Medical Center Salt Lake City, UT 84132
*Department of Medicine, the University of Tennessee, Memphis and the Research Service of the Veteran's Affairs Medical Center Memphis, TN 30104, USA
Department of Orthopedic Surgery, Kyushu University Hukuoka 814, Japan
Correspondence to:
Correspondence to: K. Terato, Department of Internal Medicine, Division of Rheumatology, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132, USA.
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 87/10 mice receiving native CII (nCII; 100 µg/mouse) alone at 9–l13 weeks. Arthritis was aggravated by the further ingestion of CII, while remission occurred after withdrawal of the CII. Heat-denatured CII (dCII; 200 µg/mouse) was also arthritogenic if co-administered with ovoinhibitor (OVI; 2 mg/mouse), a proteinase inhibitor. Co-oral administration of lipopolysaccharide (LPS; 10µg/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.
KEY WORDS: Autoantibody, Collagen-induced arthritis, Lipopolysaccharide, Mice, Mucosal permeability, NSAID, Oral immunization, Ovoinhibitor, Rheumatoid arthritis, Type II collagen
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