Prostaglandin E2 is a selective inducer of interleukin-12 p40 (IL-12p40) production and an inhibitor of bioactive IL-12p70 heterodimer

Interleukin-12 p70 (IL-12p70) heterodimer, composed of p35 and p40 subunits , is a major Th1-driving cytokine, promoting cell-mediated immunity. in con trast, IL-12p40 homodimer, secreted by APC in the absence of p35 expression , and free p40 monomer do not mediate IL-12 activity but act as IL-12 antag onists. Here it is reported that prostaglandin E-2 (PGE(2)), an inflammator y mediator with a previously known Th2-driving function, dose-dependently e nhances the IL-12p40 mRNA expression and the secretion of IL-12p40 protein in human tumor necrosis factor-alpha (TNF alpha)-stimulated immature dendri tic cells (DCs). This effect is selective and is not accompanied by the ind uction of IL-12p35 expression or by secretion of IL-12p70 heterodimer, Inab ility of TNF alpha /PGE(2) to induce IL-12p70 was not compensated by interf eron gamma (IFN gamma), which strongly enhanced the lipopolysaccharide (LPS )-induced IL-12p70 production. In addition to the selective induction of IL -12p40 in TNF alpha -stimulated Dos, PGE(2) inhibited the production of IL- 12p70 and IL-12p40 in DCs stimulated with LPS or CD40 ligand, These data su ggest an additional level of the Th2-promoting activity of PGE(2), via sele ctive induction of IL-12p40, Selective induction of IL-12p40 and suppressio n of bioactive IL-12p70 may have negative impact on anticancer vaccination with PGE(2)-matured DCs, (Blood.2001;97:3466-3469) (C) 2001 by The American Society of Hematology.