Inhibition of interleukin-17 prevents the development of arthritis in vaccinated mice challenged with Borrelia burgdorferi

Abstract

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.

FIG. 1.

Development of swelling of the hind paws of vaccinated mice with (—) and without (- - -) challenge with B. burgdorferi and with (▪) and without (□) treatment with anti-IL-17 antibody. The remaining nonvaccinated, challenged group (▵) did not receive treatment with anti-IL-17 antibody. Data are the means ± standard errors for the experiment.

FIG. 2.

Histopathology of the ankles (A, B, D, and E) and knees (C and F) of vaccinated mice challenged with B. burgdorferi with (D, E, and F) or without (A, B, and C) treatment with anti-IL-17 antibody at day 8 (A and D) and day 20 (B, C, E, and F) after infection. Controls included vaccinated, nonchallenged mice with or without treatment with anti-IL-17 antibody and nonvaccinated but challenged mice. No histopathologic changes were detected in vaccinated mice or in vaccinated, nonchallenged mice after treatment with anti-IL-17 antibody. Only minor inflammation (day 10) was observed in nonvaccinated, challenged mice. Arrows indicate areas of pannus formation (A) and no pannus formation (D).