This study was undertaken to examine the dynamic response of human peripheral blood mononuclear cells (PBMC) in the secretion of proinflammatory and anti-inflammatory cytokines induced by uromodulin (URO). Levels of tumor necrosis factor-α (TNFα), TNF soluble receptor (sTNFRI and II), interleukin 1-β (IL-1β), and IL-1 receptor antagonist (IL-1Ra) in the supernatants of URO-stimulated PBMC were measured by ELISA. URO stimulated the secretion of all these cytokines in a dose dependent manner except sTNFRI. Peak levels of TNFα and IL-1β were reached at 6–12 h, while 5–10 fold higher in sTNFR II and IL-1Ra levels were observed at 24–48 h after URO stimulation. URO-induced secretion of TNFα, IL-1β, sTNFRII and IL-1Ra could be enhanced by human plasma. Specifically, serum proteins including C3, sCD14 and IgG not only bound to URO but also enhanced URO-induced TNFα secretion of PBMC. Collectively, our data suggest that URO might have dual immunomodulating effect through regulating the secretion of proinflammatory and anti-inflammatory cytokines, and that serum binding proteins might enhance this activity.