Interleukin-18 is an essential element in host resistance to experimental group B streptococcal disease in neonates.
Previous studies demonstrated that interleukin-12 (IL-12)-dependent gamma interferon (IFN-gamma) responses have a major role in restricting in vivo bacterial growth during infection of mice with group B streptococci (GBS), important human pathogens. Like IL-12, IL-18 is a potent IFN-gamma inducer. The role of IL-18 in experimental GBS infection was investigated here. Significant elevations of IL-18 levels over baseline values were detected in plasma samples from neonatal mice rendered septic with GBS. Neutralization of IL-18 significantly increased mortality and bacterial burden (P < 0.05). In contrast, administration of recombinant IL-18 (rIL-18) before or after GBS challenge remarkably improved survival and decreased blood colony counts, in association with increased IFN-gamma production by spleen cells. The beneficial effects of rIL-18 were counteracted by administration of neutralizing anti-IFN-gamma monoclonal antibodies, indicating that the effects of IL-18 were mediated by IFN-gamma. Finally, low rIL-18 doses that had no effect of their own on bacterial burden could act in synergy with rIL-12 to protect neonatal mice during GBS infection. Collectively, our data indicate that IL-18 responses have an important role in host defenses against GBS and that rIL-18 may be useful in alternative strategies to treat neonatal GBS disease.
Cusumano
Vitaliano
V
Department of Pathology and Experimental Microbiology, Medical School, University of Messina, Messina, Italy I-98125.
Midiri
Angelina
A
Cusumano
Valentina Valeria
VV
Bellantoni
Antonella
A
De Sossi
Giuseppe
G
Teti
Giuseppe
G
Beninati
Concetta
C
Mancuso
Giuseppe
G
D000818:Animals; D000831:Animals, Newborn; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000302:isolation & purification
D020382:Interleukin-18; D011994:Recombinant Proteins; D018664:Interleukin-12