Open AccessRole of IL‐17, transforming growth factor‐β, and IL‐6 in the development of arthritis and production of anti‐outer surface protein A borreliacidal antibodies in Borrelia ‐vaccinated and ‐challenged mice
Author(s) -
Nardelli Dean T.,
Kevin Luk Kee Hang,
Kotloski Nicholas J.,
Warner Thomas F.,
Torrealba Jose R.,
Callister Steven M.,
Schell Ronald F.
Publication year - 2008
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2008.00431.x
Subject(s) - arthritis , borrelia , antibody , immune system , immunology , borrelia burgdorferi , biology , transforming growth factor , endocrinology
We showed recently that the adaptive immune events leading to the development of arthritis in Borrelia burgdorferi isolate 297‐vaccinated and Borrelia bissettii ‐challenged mice involve IL‐17. Here, we show in Borrelia ‐vaccinated and ‐challenged mice that two cytokines known to induce the production of IL‐17, IL‐6 and transforming growth factor (TGF)‐β, are also involved in the development of arthritis. Vaccinated and challenged mice administered either anti‐TGF‐β or anti‐IL‐6 antibodies developed histopathologic changes of the hind paws similar to or greater than untreated control mice. By contrast, simultaneous blockage of these cytokines reduced the severity of arthritis in Borrelia ‐vaccinated and ‐challenged mice. Moreover, administration of anti‐IL‐17 antibodies to these dual‐antibody‐treated mice completely prevented the development of histopathologic changes of the ankle joints, significantly reduced edema of the hind paws, and prevented the production of anti‐outer surface protein A borreliacidal antibodies. These findings demonstrate a role for the combined effects of IL‐17, IL‐6, and TGF‐β in the adaptive immune events leading to the development of Borrelia ‐induced arthritis.