Cytokines are suspected to play an important role in systemic infections by group B streptococci (GBS), an important cause of neonatal sepsis. This work was undertaken to determine if interleukin 12 (IL-12) is produced in mouse pups infected with GBS and has a role in this sepsis model, IL-12 elevations were measured by both an enzyme-linked immunosorbent assay and a bioassay in plasma samples obtained from 12 to 72 h after GBS challenge, Pretreatment with neutralizing anti-IL-12 antibodies significantly increased lethality and blood CFU (P < 0.05), Conversely, either prophylactically or therapeutically administered recombinant IL-12 (rIL-12) significantly improved survival time and decreased blood CFU. Since these beneficial effects were associated with increased spleen gamma interferon (IFN-gamma) production, we examined whether the latter cytokine mediated the observed rIL-12 effects. Pretreatment with neutralizing anti-IFN-gamma monoclonal antibodies significantly counteracted the beneficial effects of rIL-12 on lethality. Our data indicate that rIL-12 is a possible candidate for treatment of GBS sepsis and that its activities in this model are at least partially mediated by IFN-gamma.

Role of interleukin 12 in experimental neonatal sepsis caused by group B streptococci

MANCUSO, Giuseppe;BENINATI, Concetta;TETI, Giuseppe
1997

Abstract

Cytokines are suspected to play an important role in systemic infections by group B streptococci (GBS), an important cause of neonatal sepsis. This work was undertaken to determine if interleukin 12 (IL-12) is produced in mouse pups infected with GBS and has a role in this sepsis model, IL-12 elevations were measured by both an enzyme-linked immunosorbent assay and a bioassay in plasma samples obtained from 12 to 72 h after GBS challenge, Pretreatment with neutralizing anti-IL-12 antibodies significantly increased lethality and blood CFU (P < 0.05), Conversely, either prophylactically or therapeutically administered recombinant IL-12 (rIL-12) significantly improved survival time and decreased blood CFU. Since these beneficial effects were associated with increased spleen gamma interferon (IFN-gamma) production, we examined whether the latter cytokine mediated the observed rIL-12 effects. Pretreatment with neutralizing anti-IFN-gamma monoclonal antibodies significantly counteracted the beneficial effects of rIL-12 on lethality. Our data indicate that rIL-12 is a possible candidate for treatment of GBS sepsis and that its activities in this model are at least partially mediated by IFN-gamma.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1676120
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