Inhibition of interleukin-17 prevents the development of arthritis in vaccinated mice challenged with Borrelia burgdorferi.
We showed that Borrelia burgdorferi-vaccinated interferon gamma-deficient (IFN-gamma(0)) mice challenged with the Lyme spirochete developed a prominent chronic severe destructive osteoarthropathy. The immune response underlying the development of the severe destructive arthritis involves interleukin-17 (IL-17). Treatment of vaccinated IFN-gamma(0) mice challenged with B. burgdorferi with anti-IL-17 antibody delayed the onset of swelling of the hind paws but, more importantly, inhibited the development of arthritis. Histopathologic examination confirmed that treatment with anti-IL-17 antibody prevented the destructive arthropathy seen in vaccinated and challenged IFN-gamma(0) mice. Similar preventive results were obtained when vaccinated and challenged IFN-gamma(0) mice were treated with anti-IL-17 receptor antibody or sequentially with anti-IL-17 antibody followed by anti-IL-17 receptor antibody. By contrast, treatment of vaccinated and challenged IFN-gamma(0) mice with recombinant IL-17 (rIL-17) did not alter the development and progression of arthritis found in vaccinated and challenged IFN-gamma(0) mice without treatment with rIL-17. Therapeutic intervention may be a realistic approach to prevent arthritis, especially if IL-17 is involved in the perpetuation of chronic or intermittent arthritis.
Burchill
Matthew A
MA
Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison 53706, USA.
Nardelli
Dean T
DT
England
Douglas M
DM
DeCoster
David J
DJ
Christopherson
John A
JA
Callister
Steven M
SM
Schell
Ronald F
RF
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001428:Bacterial Vaccines / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000502:physiology; D008193:Lyme Disease / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000633:toxicity; D014611:Vaccination
D000906:Antibodies; D001428:Bacterial Vaccines; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D007371:Interferon-gamma