AbstractLeIF, a gene homologue of the eukaryotic initiation factor 4A was first described as a leishmanial antigen that induced a Th1‐type T cell response in peripheral blood mononuclear cells (PBMC) from leishmaniasis patients. Moreover, the interferon (IFN)‐γ production by PBMC was found to be interleukin (IL)‐12 dependent. Herein, we characterize the effects of LeIF on cytokine production and expression of surface molecules by normal human monocytes as well as by monocyte‐derived macrophages and dendritic cells (MoDC). LeIF was a strong inducer of IL‐12 and, to a lesser extent, of IL‐10 and tumor necrosis factor (TNF)‐α in macrophages and MoDC. IL‐12 production did not require CD40 triggering, confirming that the ability of LeIF to induce IL‐12 was not mediated through an effect on T cells. However, addition of soluble CD40 ligand (L) synergistically augmented IL‐12 production in macrophages and MoDC. The cytokine‐inducing activity of LeIF is located in the N‐terminal portion of the molecule and was both proteinase K sensitive and polymyxin B resistant. LeIF, lipopolysaccharide and fixed Staphylococcus aureus all induced comparable amounts of IL‐12, validating the potent cytokine‐inducing effects of LeIF. Moreover, of these stimuli, LeIF had the highest IL‐12/IL‐10 and IL‐12/TNF‐α ratio demonstrating the preference of LeIF for IL‐12 induction. Studies investigating the expression of surface molecules showed that LeIF up‐regulated B7‐1 and CD54 (ICAM‐1) on macrophages and MoDC. To our knowledge this is the first report describing IL‐12 production, up‐regulation of co‐stimulatory and intercellular adhesion molecules by monocytic antigen‐presenting cells in response to a protein from a pathogenic microorganism. These immunomodulatory characteristics of LeIF might be excellent properties for a Th1‐type adjuvant.