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Clinical and Diagnostic Laboratory Immunology, January 2003, p. 44-52, Vol. 10, No. 1
1071-412X/03/$08.00+0 DOI: 10.1128/CDLI.10.1.44-52.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Douglas M. England,3,4 Cindy L. Croke,1,2 Monica C. Remington,1,2 Melanie L. Molitor,1,2 David J. DeCoster,1,2 Steven M. Callister,5,6 and Ronald F. Schell1,2,7*
Wisconsin State Laboratory of Hygiene,1 Departments of Medical Microbiology and Immunology,2 Pathology and Laboratory Medicine,3 Bacteriology, University of Wisconsin, Madison, Wisconsin 53706,7 Department of Pathology, Meriter Hospital, Madison, Wisconsin 53715,4 Microbiology Research Laboratory,5 Department of Infectious Diseases, Gundersen Lutheran Medical Center, La Crosse, Wisconsin 546016
Received 19 June 2002/ Returned for modification 29 August 2002/ Accepted 26 September 2002
We found that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-
0) mice challenged with B. burgdorferi developed prominent chronic destructive osteoarthropathy. When these mice were treated with anti-tumor necrosis factor alpha (TNF-
) antibody, the severity of the destructive osteoarthritis was enhanced and affected the mobility of the animals. In addition, extensive swelling of the hind paws occurred. In contrast, treatment of B. burgdorferi-vaccinated, challenged IFN-
0 mice with recombinant TNF-
(rTNF-
) inhibited the development of arthritis, including swelling of the hind paws. Moreover, treatment of vaccinated, challenged IFN-
0 mice with anti-TNF-
inhibited fourfold the production of an antibody that kills B. burgdorferi, while treatment of vaccinated, challenged IFN-
0 mice with rTNF-
slightly elevated the level of the borreliacidal antibody. These results suggest that the level of TNF-
directly or indirectly regulates the production of borreliacidal antibody and the development of vaccine-induced destructive Lyme osteoarthritis. Studies are in progress to determine the mechanism by which TNF-
-dependent cytokines generate the destructive arthritis.
Present address: Medical Science Laboratories, Wauwatosa, WI 53226.
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