Role of interleukin 12 in experimental neonatal sepsis caused by group B streptococci.
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.
Mancuso
G
G
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
Cusumano
V
V
Genovese
F
F
Gambuzza
M
M
Beninati
C
C
Teti
G
G
D000818:Animals; D000831:Animals, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000503:physiopathology*; D013290:Streptococcal Infections / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma