IFN-beta and TGF-beta differentially regulate IL-12 activity in human peripheral blood mononuclear cells

Both IFN-beta and TGF-beta have demonstrated their ability to antagonize se veral of the stimulatory activities of IFN-gamma on human macrophages, ther eby classifying them as Th2-like. Aiming at a further characterization of t heir rule in Th1/Th2 development, we studied their possible interaction wit h IL-12, the key Th1 cytokine. We found that IFN-beta by itself induced mod est amounts of IFN-gamma, but was able to synergize with IL-12 for IFN-gamm a induction. TGF-beta, on the other hand, had no effect by itself and inhib ited significantly the IL-12-induced IFN-gamma secretion. The differential effect of IFN-beta and TGF-b on IL-12 bioactivity was most pronounced upon IFN-gamma synthesis, since IFN-beta induced only marginal amounts of IL-10 and IL-12 and TGF-beta diminished constitutive IL-10 production, while neit her had a significant effect on TNF-alpha production. Although monocytes di d not produce detectable IFN-gamma with any of the stimuli, adherent cells were found to cooperate with non-adherent lymphocytes for maximal IFN-gamma production. However, IL-18, a monocyte-derived IFN-gamma -inducing cytokin e able to synergize with IL-12, was undetectable in IFN-beta or IFN-beta IL-12-stimulated cells. In conclusion, the ability of IFN-beta to synergize with IL-12 for IFN-gamma synthesis, without significant concomitant IL-10 production, suggest a strong boost to Th1 development, which seems to be IL -18-independent. (C) 2001 Elsevier Science B.V. All rights reserved.