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

Abstract

We showed thatArthritis is a frequent and major complication of natural and experimental infection with Borrelia burgdorferi (1,5,30,34). Moreover, arthritis is induced following vaccination, with (14, 25) or without (28) challenge with B. burgdorferi. The immunologic events responsible for these B. burgdorferi-associated arthritides are poorly understood. We demonstrated that induction of chronic severe destructive arthritis following vaccination and challenge was dependent on B. burgdorferi-specific T lymphocytes (23). Treatment of vaccinated animals with anti-CD4 antibody prevented the development of severe destructive arthritis when the animals were challenged with the Lyme spirochete (24). Activated or primed CD4 ϩ T cells participated in the development of arthritis that included cartilage and bone erosion (24).Recently, we also showed that B. burgdorferi-vaccinated interferon gamma-deficient (IFN-␥ 0 ) mice challenged with B. burgdorferi developed a prominent chronic severe destructive osteoarthropathy (12). These results along with those of Brown and Reiner (6) present compelling evidence that interferon gamma (IFN-␥) does not play a major role in the induction or propagation of arthritis in the infection (6) or vaccinationchallenge (12) model of B. burgdorferi-associated arthritis. This suggests that other cytokines, chemokines, or other immune regulators are responsible for the induction of arthritis.

Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

“…We further showed that the significant hind paw swelling and histopathological changes observed in B. burgdorferi-infected, IL-10-deficient mice were partially inhibited by administration of anti-IL-17 antibody. Collectively, these findings support our claims (12)(13)(14)(15)(16)(17)23) and those of Stimulated cells from uninfected wild-type mice also produced significantly more IL-17 than stimulated cells from uninfected IL-10-deficient mice. In addition, in vitro stimulation with B. burgdorferi for 6 h caused a significant decrease in IL-17 production by cells from IL-10-deficient, but not wild-type, mice, regardless of whether the mice were previously infected.…”

“…Infante-Duarte et al first determined that stimulated cells of Lyme arthritis patients produce IL-17 (18). Following this observation, a series of studies showed that various Th17-associated cytokines were associated with pathology in murine models of Borrelia-induced arthritis (12)(13)(14)(15)(16)(17), supporting claims of the arthritic potential of IL-17 in Lyme arthritis (23). Supporting this, NapA of B. burgdorferi stimulated innate cells to drive the development of Th17 cells that were present in the synovia of humans with Lyme arthritis (19).…”

“…The pathology of disease in humans is driven, in large part, by Th1 cells and their prototypical inflammatory cytokine, gamma interferon (IFN-␥) (5)(6)(7)(8). However, studies with multiple animal models have shown that a Th1 response is not absolutely necessary for the development of arthritis after B. burgdorferi infection (9)(10)(11), while the inflammatory cytokine interleukin-17 (IL-17) contributes to disease (12)(13)(14)(15). Specifically, blocking IL-17 and various Th17-associated cytokines in vivo reduced the severity of arthritis observed in models of Borrelia-associated arthritis in the presence (15)(16)(17) or absence (12)(13)(14) of IFN-␥.…”

Do Behçet's syndrome patients with acne and arthritis comprise a true subset? Comment on the article by Hatemi et al

“…The issue of whether Behçet's syndrome should be classified among the spondylarthritides (SpA) has become the subject of lively debate, with some groups completely opposed to the hypothesis (1,2) and others strongly supporting it (3,4). In their recent article, Hatemi and colleagues took the latter position (5).…”

“…In summary, the studies by Codolo and colleagues (1) and those using the Borrelia vaccination and challenge model of Lyme arthritis (3)(4)(5)(6)(7)(8) can be used to further explore the complex immunologic pathways responsible for the development and resolution of Lyme arthritis.…”