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Infection and Immunity, June 2003, p. 3437-3442, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3437-3442.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Inhibition of Interleukin-17 Prevents the Development of Arthritis in Vaccinated Mice Challenged with Borrelia burgdorferi

Matthew A. Burchill,1,2 Dean T. Nardelli,1,2 Douglas M. England,3,4 David J. DeCoster,1,5 John A. Christopherson,1,5 Steven M. Callister,6 and Ronald F. Schell1,2,5*

Wisconsin State Laboratory of Hygiene,1 Departments of Bacteriology,2 Medical Microbiology and Immunology,5 Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53706,3 Department of Pathology, Meriter Hospital, Madison, Wisconsin 53715,4 Microbiology Research Laboratory and Department of Infectious Diseases, Gundersen Lutheran Medical Center, La Crosse, Wisconsin 546016

Received 1 October 2002/ Returned for modification 16 January 2003/ Accepted 12 March 2003

We showed that Borrelia burgdorferi-vaccinated interferon gamma-deficient (IFN-{gamma}0) mice challenged with the Lyme spirochete developed a prominent chronic severe destructive osteoarthropathy. The immune response underlying the development of the severe destructive arthritis involves interleukin-17 (IL-17). Treatment of vaccinated IFN-{gamma}0 mice challenged with B. burgdorferi with anti-IL-17 antibody delayed the onset of swelling of the hind paws but, more importantly, inhibited the development of arthritis. Histopathologic examination confirmed that treatment with anti-IL-17 antibody prevented the destructive arthropathy seen in vaccinated and challenged IFN-{gamma}0 mice. Similar preventive results were obtained when vaccinated and challenged IFN-{gamma}0 mice were treated with anti-IL-17 receptor antibody or sequentially with anti-IL-17 antibody followed by anti-IL-17 receptor antibody. By contrast, treatment of vaccinated and challenged IFN-{gamma}0 mice with recombinant IL-17 (rIL-17) did not alter the development and progression of arthritis found in vaccinated and challenged IFN-{gamma}0 mice without treatment with rIL-17. Therapeutic intervention may be a realistic approach to prevent arthritis, especially if IL-17 is involved in the perpetuation of chronic or intermittent arthritis.

* Corresponding author. Mailing address: University of Wisconsin, Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706. Phone: (608) 262-3634. Fax: (608) 265-3451. E-mail: RFSchell{at}facstaff.wisc.edu.

Editor: V. J. DiRita

Infection and Immunity, June 2003, p. 3437-3442, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3437-3442.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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