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Destructive arthritis in vaccinated interferon gamma-deficient mice challenged with Borrelia burgdorferi: modulation by tumor necrosis factor alpha.

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By Christopherson JA, Munson EL, England DM, Croke CL, Remington MC, Molitor ML, DeCoster DJ, Callister SM, Schell RF • www.ProHealth.com • January 1, 2003


Abstract

We found that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-gamma(0)) mice challenged with B. burgdorferi developed prominent chronic destructive osteoarthropathy. When these mice were treated with anti-tumor necrosis factor alpha (TNF-alpha) 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-gamma(0) mice with recombinant TNF-alpha (rTNF-alpha) inhibited the development of arthritis, including swelling of the hind paws. Moreover, treatment of vaccinated, challenged IFN-gamma(0) mice with anti-TNF-alpha inhibited fourfold the production of an antibody that kills B. burgdorferi, while treatment of vaccinated, challenged IFN-gamma(0) mice with rTNF-alpha slightly elevated the level of the borreliacidal antibody. These results suggest that the level of TNF-alpha 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-alpha-dependent cytokines generate the destructive arthritis.

Clin Diagn Lab Immunol. 2003 Jan;10(1):44-52.





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