Experimental lyme arthritis in the absence of interleukin-4 or gamma interferon.
Genetic resistance and susceptibility to experimental Lyme arthritis have been linked with the production of interleukin-4 (IL-4) or gamma interferon (IFN-gamma), respectively. To determine the absolute requirement for these cytokines in disease outcome, we compared arthritis development in wild-type, IL-4-deficient (IL-4 degrees ), and IFN-gamma-deficient (IFN-gamma degrees ) mice. While susceptible C3H mice developed swelling of ankle joints during the second week of infection, this swelling was exacerbated in C3H IFN-gamma degrees mice. Their arthritis severity scores at day 21, however, were similar. Resolution of arthritis was also similar between C3H and C3H IFN-gamma degrees mice. Arthritis-resistant DBA mice did not develop ankle swelling during the experimental period. There were no differences in ankle swelling or arthritis severity scores between control DBA mice and DBA IL-4 degrees mice at any of the time points tested. While the presence of spirochetes in various tissues was similar among all strains at day 21, DBA IL-4 degrees mice had a higher presence of spirochetes in blood, heart, and spleen than the DBA, C3H, and C3H IFN-gamma degrees mice did at day 60. DBA IL-4 degrees mice also had impaired ability to produce Borrelia-specific antibody responses, especially immunoglobulin G1. Thus, while IFN-gamma and IL-4 are not absolutely required for arthritis susceptibility or resistance, the production of IL-4 does appear to play an important role in Borrelia-specific antibody production and spirochete clearance.
Brown
C R
CR
Department of Medicine and Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
Reiner
S L
SL
D000818:Animals; D015748:Borrelia burgdorferi Group / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D008193:Lyme Disease / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout
D015847:Interleukin-4; D007371:Interferon-gamma