Regulatory role of interleukin-10 in experimental group B streptococcal arthritis.
Intravenous inoculation of CD-1 mice with 10(7) CFU of type IV group B Streptococcus (GBS) results in a high incidence of diffuse septic arthritis, associated with high levels of systemic and local production of interleukin-1beta (IL-1beta) and IL-6. In this study, the role of the anti-inflammatory cytokine IL-10 in the evolution of GBS systemic infection and arthritis was evaluated. IL-10 production was evident in sera and joints of GBS-infected mice. Neutralization of endogenous IL-10 by administration of anti-IL-10 antibodies (1 mg/mouse) at the time of infection resulted in worsening of articular lesions and 60% mortality associated with early sustained production of IL-6, IL-1beta, and tumor necrosis factor alpha (TNF-alpha). The effect of IL-10 supplementation was assessed by administering IL-10 (100, 200, or 400 ng/mouse) once a day for 5 days, starting 1 h after infection. Treatment with IL-10 had a beneficial effect on GBS arthritis, and there was a clear-cut dose dependence. The decrease in pathology was associated with a significant reduction in IL-6, IL-1beta, and TNF-alpha production. Histological findings showed limited periarticular inflammation and a few-cell influx in the articular cavity of IL-10-treated mice, confirming clinical observations. In conclusion, this study provides further information concerning the role of IL-10 in regulating the immune response and inflammation and calls attention to the potential therapeutic use of IL-10 in GBS arthritis.
Puliti
Manuela
M
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Von Hunolstein
Christina
C
Verwaerde
Claudie
C
Bistoni
Francesco
F
Orefici
Graziella
G
Tissi
Luciana
L
D000818:Animals; D001170:Arthritis, Infectious / Q000097:blood / Q000276:immunology* / Q000401:mortality; D004195:Disease Models, Animal; D005260:Female; D007375:Interleukin-1 / Q000276:immunology; D016753:Interleukin-10 / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D013290:Streptococcal Infections / Q000097:blood / Q000276:immunology* / Q000401:mortality; D013292:Streptococcus agalactiae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10