The beneficial effect of interleukin-12 on arthritis induced by group B streptococci is mediated by interferon-gamma and interleukin-10 production.
OBJECTIVE
To assess the effect of interleukin-12 (IL-12) administration on the evolution of systemic infection and septic arthritis induced by group B streptococci (GBS) in mice.


METHODS
CD1 mice were inoculated intravenously with arthritogenic strain 1/82 of type IV GBS. Exogenous murine IL-12 was administered intraperitoneally 18 hours or 5 days after infection with 1 x 10(7) GBS, at doses ranging from 0.5 to 2.5 microg per mouse. Mice were monitored daily for survival and for signs of arthritis. In a subsequent set of experiments, mice were killed at selected times for examination of bacterial clearance, histopathologic changes in the joints, and cytokine production.


RESULTS
IL-12 administration before the onset of clinical signs had a beneficial effect on GBS-induced arthritis and was clearly dose-dependent. The 2.5-microg dose per mouse totally prevented death from GBS-induced arthritis. The decrease in pathology was associated with a reduction of the bacterial burden and a change in the cytokine profile. In particular, systemic and joint levels of interferon-gamma (IFN gamma) and IL-10 significantly increased in mice treated with IL-12, whereas a decrease in IL-6 and IL-1 beta production was observed. The beneficial effects of IL-12, in terms of the incidence and severity of articular lesions, were reversed by coadministration of anti-IFN gamma or anti-IL-10-neutralizing antibodies.


CONCLUSIONS
The findings of this study demonstrate that IL-12 is important in controlling the cytokine production that leads to the evolution of GBS-induced experimental arthritis. The amelioration of articular lesions is mostly attributable to IL-12-induced IFN gamma, but with a relevant participation of IL-12-induced IL-10.
Puliti
Manuela
M
University of Perugia, Perugia, Italy.
von Hunolstein
Christina
C
Bistoni
Francesco
F
Mosci
Paolo
P
Orefici
Graziella
G
Tissi
Luciana
L
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D021461:Animals, Outbred Strains; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality / Q000503:physiopathology; D001769:Blood / Q000382:microbiology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000502:physiology; D018664:Interleukin-12 / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D007958:Leukocyte Count; D051379:Mice; D013290:Streptococcal Infections; D013292:Streptococcus agalactiae / Q000302:isolation & purification
D000276:Adjuvants, Immunologic; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma