Role of interleukin-18 in experimental group B streptococcal arthritis.
OBJECTIVE
To assess the role of interleukin-18 (IL-18) in the evolution of septic arthritis induced by group B streptococci (GBS) in mice.


METHODS
CD1 mice were inoculated intravenously with 8 x 10(6) colony-forming units (CFU) of type IV GBS (strain 1/82), and administered intraperitoneally 1 hour before infection with anti-IL-18 monoclonal antibodies (0.25 mg/mouse). In a subsequent set of experiments, mice infected with a suboptimal arthritogenic dose of GBS (4 x 10(6) CFU/mouse) were administered different doses of recombinant IL-18 for 4 days, starting 1 hour after infection. Mortality, evolution of arthritis, bacterial clearance, joint histopathology, and cytokine production were examined in infected mice that did or did not receive treatment with anti-IL-18 antibodies or IL-18.


RESULTS
IL-18 was produced during GBS infection. Neutralization of IL-18 resulted in a decrease in mortality rates, and in the incidence and severity of arthritis. Amelioration of arthritis was accompanied by a dramatic reduction in local IL-1 beta, IL-6, macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-2 production, and reduced bacterial burden. Administration of exogenous IL-18 resulted in increased mortality rates and increased incidence and severity of GBS arthritis, concomitant with a higher number of GBS and increased levels of IL-6, IL-1 beta, MIP-1 beta, and MIP-2 production in the joints.


CONCLUSIONS
The present study indicated some involvement of IL-18 in the pathogenesis of GBS-induced arthritis. The role of IL-18 in joint pathology is shown by a regulatory effect on inflammatory mediator levels and local cell influx. Thus, IL-18 should be regarded as a potential therapeutic target in GBS infection and arthritis.
Tissi
Luciana
L
Department of Experimental Medicine and Bichemical Sciences, University of Perugia, Perugia, Italy. tissi@unipg.it
McRae
Bradford
B
Ghayur
Tariq
T
von Hunolstein
Christina
C
Orefici
Graziella
G
Bistoni
Francesco
F
Puliti
Manuela
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001170:Arthritis, Infectious / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015994:Incidence; D020382:Interleukin-18 / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012720:Severity of Illness Index; D013290:Streptococcal Infections / Q000150:complications / Q000276:immunology* / Q000401:mortality; D013292:Streptococcus agalactiae / Q000276:immunology*
D000906:Antibodies; D016207:Cytokines; D020382:Interleukin-18