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• W4313335045 endingPage "4252" @default.
• W4313335045 startingPage "4246" @default.
• W4313335045 abstract "Abstract Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been accepted as the most effective agent in clinical use against superficial bladder cancer, its mechanism of action remains incompletely understood. A kinetic analysis in assessing the potential role of cytokines from BCG-stimulated murine splenocytes showed that IL-12 expression preceded that of other cytokines. Experiments subtracting endogenous BCG-driven IL-12 using neutralizing Ab or augmenting its activity with supplemental rIL-12 revealed not only that IL-12 plays a dominant role in IFN-γ induction but also that it is normally dose limiting. A striking increase in IFN-γ production could be generated in both mouse and human immunocompetent cell culture by the addition of even a small amount of rIL-12. Moreover, this same synergistic effect could be replicated during in vivo administration of BCG plus rIL-12 into the mouse bladder and was observed in a patient receiving intravesical combination therapy. In costimulation cultures, this synergy appeared to partially rely on IL-18 and IL-2 and could be down-regulated by IL-10. This suggests that a dynamic interplay between Th1 and Th2 cytokines is responsible for net IFN-γ production. The ability of supplemental exogenous IL-12 to strongly shift this balance toward Th1 provides an immunological basis for using it in conjunction with intravesical BCG for bladder cancer immunotherapy." @default.
• W4313335045 created "2023-01-06" @default.
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• W4313335045 date "1999-10-15" @default.
• W4313335045 modified "2023-10-14" @default.
• W4313335045 title "Role of IL-12 in the Induction and Potentiation of IFN-γ in Response to Bacillus Calmette-Guérin" @default.
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• W4313335045 doi "https://doi.org/10.4049/jimmunol.163.8.4246" @default.
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