Identification of a rat bone marrow-derived dendritic cell population which secretes both IL-10 and IL-12: evidence against a reciprocal relationship between IL-10 and IL-12 secretion.

ABSTRACT

The qualitative nature of immune responses induced by dendritic cells (DCs) is influenced by the balance of pro-inflammatory (e.g. IL-12) and anti-inflammatory (e.g. IL-10) cytokines that they secrete. Evidence to date suggests that IL-12 and IL-10 secretion is reciprocally regulated and that IL-10 inhibits IL-12 secretion. This study identifies a population of resting, immature rat bone marrow-derived DCs (BMDCs) which secretes IL-10, the IL-12(p70) heterodimer and the free IL-12(p40) subunit, the latter in vast excess of IL-12(p70). Counter-intuitively, activation with LPS induces the secretion of high and equivalent levels of IL-10 and IL-12(p40), but only quantitatively small increases in IL-12(p70). Neutralization of IL-10 increased the secretion of IL-12(p40) by resting BMDCs, but decreased IL-12(p40) secretion by LPS-activated BMDCs. Pre-incubation of resting BMDCs for 24h with neutralizing antibody to IL-10 reduced the subsequent secretion of IL-10 in allogeneic cultures of Lewis CD3(+) T cells with resting and LPS-activated Wistar BMDCs, and enhanced IL-12(p40) secretion in allogeneic cultures with LPS-activated BMDCs. IL-10 neutralization had no effect on the levels of IL-12(p70), IFN-gamma or IL-4 in allogeneic cultures. In summary, this study has identified a population of rat BMDCs that secretes low levels of bioactive IL-12(p70), but high levels of IL-10 and IL-12(p40). These findings argue against the concept that there is a reciprocal relationship between IL-10 and IL-12 secretion. They might also have implications for understanding the role of DCs in post-activation qualitative skewing of immune responses.