Adenoviral delivery of interleukin-10 fails to attenuate experimental Lyme disease.
Production of interleukin-10 (IL-10) by C57BL/6 mice following infection with Borrelia burgdorferi has been proposed as a mechanism whereby resistance to the development of experimental Lyme arthritis is maintained. In the current study, we sought to determine the role of IL-10 during infection of arthritis- and carditis-susceptible C3H mice. Infection of C3H IL-10(-/-) mice led to increased joint swelling and arthritis severity scores over those of wild-type C3H mice. Measurement of B. burgdorferi numbers in joints or disseminated tissues indicated a more efficient clearance of spirochetes in the absence of IL-10, similar to that reported in C57BL/6 IL-10(-/-) mice. However, in contrast to previous in vitro work, infection of C3H IL-10(-/-) mice led to decreased in vivo expression of the cytokines KC, IL-1beta, IL-4, and IL-12p70 in the infected joints. Finally, adenoviral expression of IL-10 in the infected joints of C3H mice was unable to modulate the development of severe Lyme arthritis and had no effect on spirochete clearance or Borrelia-specific antibody production. Development of Lyme carditis appeared to be independent of modulation by IL-10. These results suggest that IL-10 limits the development of joint inflammation in both arthritis-resistant and -susceptible mouse strains infected with B. burgdorferi and that increased IL-10 production cannot rescue genetic susceptibility to development of pathology in this model.
Brown
Charles R
CR
Department of Veterinary Pathobiology, 315 Connaway Hall, University of Missouri, Columbia, MO 65211, USA. Brownchar@missouri.edu
Lai
Annie Y-C
AY
Callen
Steven T
ST
Blaho
Victoria A
VA
Hughes
Jennifer M
JM
Mitchell
William J
WJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D025065:Borrelia burgdorferi; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009205:Myocarditis / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D016207:Cytokines; D016753:Interleukin-10