Previous studies demonstrated that interleukin-12 (IL-12)-dependent gamma interferon (IFN-) 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- 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- production by spleen cells. The beneficial effects of rIL-18 were counteracted by administration of neutralizing anti-IFN- monoclonal antibodies, indicating that the effects of IL-18 were mediated by IFN-. 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.
Interleukin-18 is an essential element in host resistance to experimental group B streptococcal disease in neonates
CUSUMANO, Vitaliano;MIDIRI, Angelina;TETI, Giuseppe;BENINATI, Concetta;MANCUSO, Giuseppe
2004-01-01
Abstract
Previous studies demonstrated that interleukin-12 (IL-12)-dependent gamma interferon (IFN-) 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- 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- production by spleen cells. The beneficial effects of rIL-18 were counteracted by administration of neutralizing anti-IFN- monoclonal antibodies, indicating that the effects of IL-18 were mediated by IFN-. 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.Pubblicazioni consigliate
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