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-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.
Christopherson
John A
JA
Wisconsin State Laboratory of Hygiene, Department of Medical Microbiology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Munson
Erik L
EL
England
Douglas M
DM
Croke
Cindy L
CL
Remington
Monica C
MC
Molitor
Melanie L
ML
DeCoster
David J
DJ
Callister
Steven M
SM
Schell
Ronald F
RF
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood / Q000187:drug effects; D001168:Arthritis / Q000139:chemically induced* / Q000473:pathology; D001428:Bacterial Vaccines / Q000009:adverse effects*; D025065:Borrelia burgdorferi / Q000276:immunology; D004357:Drug Synergism; D007371:Interferon-gamma; D008193:Lyme Disease / Q000150:complications*; D051379:Mice; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma