Destructive Arthritis in Vaccinated Interferon Gamma-Deficient Mice Challenged with Borrelia burgdorferi: Modulation by Tumor Necrosis Factor Alpha

We found that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-γ(0)) mice challenged with B. burgdorferi developed prominent chronic destructive osteoarthropathy. When these mice were treated with anti-tumor necrosis factor alpha (TNF-α) antibody, the severity of the destructive osteoarthritis was enhanced and affected the mobility of the animals. In addition, extensive swelling of the hind paws occurred. In contrast, treatment of B. burgdorferi-vaccinated, challenged IFN-γ(0) mice with recombinant TNF-α (rTNF-α) inhibited the development of arthritis, including swelling of the hind paws. Moreover, treatment of vaccinated, challenged IFN-γ(0) mice with anti-TNF-α inhibited fourfold the production of an antibody that kills B. burgdorferi, while treatment of vaccinated, challenged IFN-γ(0) mice with rTNF-α slightly elevated the level of the borreliacidal antibody. These results suggest that the level of TNF-α directly or indirectly regulates the production of borreliacidal antibody and the development of vaccine-induced destructive Lyme osteoarthritis. Studies are in progress to determine the mechanism by which TNF-α-dependent cytokines generate the destructive arthritis.