Effect of different activation stimuli on the cytokine response of human macrophages to CD40L.

Here we show that CD40L (ligand for CD40) failed to induce the production of tumour necrosis factor alpha (TNF-alpha), interleukin (IL-)-1 beta, IL-10 and IL-12 in macrophages matured in vitro in the absence of growth factors or in the presence of macrophage colony-stimulating factor (M-CSF). In contrast, enzyme-linked immunoabsorbent assay (ELISA) testing and cytofluorimetric (FACS) analysis demonstrated significant production of TNF-alpha and IL-1 beta, but not of IL-10 and IL-12 in macrophages maturated in the presence of CD40L and re-stimulated with CD40L. The priming effect of CD40L on TNF-alpha and IL-1 beta production was related to induction of CD40 expression. Finally, CD40L priming did not modify the cytokine response of macrophages to lipopolysaccharide. In conclusion, our results suggest that CD40/CD40L interactions are important for the activation of macrophages as effector cells that mediate inflammation and tissue damage in T cell-mediated inflammatory processes.