Borrelia-primed and -infected mice deficient of interleukin-17 develop arthritis after neutralization of gamma-interferon.
The immune mechanisms responsible for development of Lyme arthritis are partially understood with interleukin-17 (IL-17) and gamma-interferon (IFN-γ) playing a generally accepted role. Elevated levels of IL-17 and/or IFN-γ have been reported in samples from human Lyme arthritis patients and experimental mice. In addition, IL-17 and IFN-γ have been implicated in the onset of arthritis in Borrelia-primed and -infected C57BL/6 mice. Recently, we showed that IL-17-deficient mice developed swelling and histopathological changes consistent with arthritis in the presence of high levels of IFN-γ. We hypothesized that neutralization of IFN-γ in IL-17-deficient mice would inhibit Borrelia-induced arthritis. Our results, however, showed that swelling of the hind paws and histopathological changes of arthritis did not differ between Borrelia-primed and -infected IL-17-deficient and wild-type mice with or without neutralization of IFN-γ. We also found higher levels of tumor necrosis factor alpha (TNF-α) and IL-6 in the popliteal lymph node cells of Borrelia-primed and -infected IL-17-deficient mice after neutralization of IFN-γ. These results suggest that multiple cytokines interact in the development of Borrelia-induced arthritis.
Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison, Madison, WI 53706, USA.|Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Joseph
J
Kuo
Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
Thomas F
TF
Warner
Wisconsin State Laboratory of Hygiene, University of Wisconsin-Madison, Madison, WI 53706, USA.|Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.|Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Ronald F
RF
Schell
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001168:Arthritis / Q000209:etiology* / Q000473:pathology; D001898:Borrelia / Q000276:immunology*; D001899:Borrelia Infections / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020381:Interleukin-17 / Q000172:deficiency*; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D000911:Antibodies, Monoclonal; D016207:Cytokines; D020381:Interleukin-17; D007371:Interferon-gamma
Borrelia burgdorferi; Lyme arthritis; T cells; gamma-interferon; interleukin-17; interleukin-6; tumor necrosis factor alpha