In order to investigate the impact of an inflamatory mediator PGE₂ on the functions of maturing DC we used an in vitro model of DC generation from peripheral blood monocytes. Addition of PGE, (10⁻⁹M–10⁻⁶M) to the cultures performed in the presence of GM-CSF and IL-4 did not alter the morphology nor high levels of expression of class II MHC and co-stimulatory molecules on arising DC, although at concentrations above 10⁻⁸ M, the acquisition of CD1a was selectively prevented. Control DC and the DC maturing in the presence of PGE₂ (PGE,-DC) induced a similar proliferation of naive Th cells. Control DC produced high amounts of IL-12, and only trace amounts of IL-10, whereas PGE₂-DC produced no IL-12 and high levels of IL-10, when stimulated after the removal of PGE₂. The deficient IL-12 production by PGE₂-DC was observed after stimulation both in the absence and in the presence of IFNy, and was not compensated during further 48 h culture in the absence of PGE₂. Compared to control DC, PGE₂-DC induced development of Th cells secreting elevated amounts of IL-4 and IL-5, from naive precursors. These data indicate that elevated tissue levels of PGE, may promote type 2 Th responses by impairing the ability of locally maturing DC to produce IL-12. Since Th2 responses mediate protection in Thl-related autoimmune disorders, the use of PGE₂-DC in immunotherapy of such disorders may be considered.