The effects of interleukin-4 and interferon-gamma on borreliacidal antibody productio

The morbidity associated with Lyme borreliosis has provided impetus for development of a vaccine for prevention of Borrelia burgdorferi (Bb) infection. Induction of borreliacidal antibody is paramount for establishing the effectiveness of Lyme borreliosis vaccines. Vaccine preparations incorporating recombinant (r) outer surface protein A (OspA) of Bb induced borreliacidal antibody, however, the duration of protection was limited.;We sought to develop an in vitro system to determine the effects of cytokines, specifically interleukin (IL)-4 and interferon-gamma (IFN-gamma), on borreliacidal antibody production. Lymph node cells (LNC) obtained from C3H/HeJ mice vaccinated against Bb were cultured with macrophages and Bb. Anti-OspA borreliacidal antibody was detected in supernatants of cultures of LNC obtained on day 7 after vaccination, peaked on day 17, and rapidly declined. The borreliacidal antibody response was due to IgG1, IgG2a, and IgG2b antibodies. Production of anti-OspA borreliacidal antibody was inhibited, however, when anti-OspA borreliacidal antibody producing cells (BAPC) were treated with rIL-4. Furthermore, treatment of anti-OspA BAPC with anti-IL-4 failed to alter borreliacidal antibody production.;The inability of IL-4-stimulated immune LNC to increase production of borreliacidal antibody may be due to down-regulation of IFN-gamma. When BAPC were exposed to rIFN-gamma, borreliacidal antibody production was suppressed. Suppression of borreliacidal antibody was not greatly affected by the time of rIFN-gamma, treatment. In addition, treatment with rIFN-gamma, inhibited the production of other anti-Bb antibodies. These results show that IFN-gamma does not play a major role in the production of borreliacidal antibody.;By contrast, treatment of BAPC with anti-IFN-gamma augmented borreliacidal antibody production eight-fold. However, treatment of BAPC with anti-IFN-gamma also increased their ability to induce arthritis. When BAPC treated with anti-IFN-gamma were infused into immunocompetent C3H/Hej mice, they developed severe destructive Lyme arthritis. Histopathologic examination showed that severe erosion of bone had occurred.;Collectively, these results show that treatment of BAPC with anti-IFN-gamma-augments both cidal antibody production and ability of these cells to induce arthritis. Additional studies are needed to determine which cytokine(s) augments borreliacidal antibody production in anti-IFN-gamma-treated BAPC without enhancing the development of arthritis. These studies are necessary to ensure a safe and comprehensive vaccine against Bb infection.