IL-1β induces dendritic cells to produce IL-12

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Abstract
The cytokine IL-12, a product of dendritic cells (DC), plays a major role in cellular immunity, notably by inducing lymphocytes to produce IFN-γ. Microbial products, T cell signals and cytokines induce the production of IL-12. Here, IL-1β is identified as a new IL-12-inducing agent, acting conjointly with CD40 ligand (CD40L) on human monocyte-derived DC in vitro. The effects of IL-1β were dose dependent, specifically blocked by neutralizing antibodies, and were observed both in immature and mature DC. Immature DC secreted more IL-12 than mature DC, but the effects of IL-1β were not due to a block of DC maturation as determined by analysis of DC surface markers. The mechanisms of action of IL-1β could be contrasted to that of other inducers of IL-12 such as IFN-γ and lipopolysaccharide (LPS). Either IL-1β or IFN-γ co-induced IL-12 with CD40L but conjointly, IL-1β, CD40L and IFN-γ synergized, inducing very high levels of IL-12. The effects of IL-1β differed from those of LPS in that IL-1β, unlike LPS, could not induce IL-12 solely after IFN-γ priming; and when combined with CD40L, IL-1β, unlike LPS, induced little IL-10. The mechanism of action of IL-1β involves IL-12α mRNA up-regulation, and we show that the combination of CD40L and IL-1β induces high levels of IL-12α and IL-12β mRNA in DC. Altogether, these results delineate a new mechanism linking adaptive and innate immune responses for the regulation of IL-12 production in DC and for the role of IL-1β in the development of cellular immunity.

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