The purpose of this study was to determine if P-selectin, an adhesion molecule involved in the transendothelial movement of leukocytes, might also have a direct influence on the function of cells that come into contact with it. Human peripheral blood mononuclear cells were incubated on immobilized P-selectin or a control substrate (bovine serum albumin, BSA) and stimulated with bacterial lipopolysaccharide (LPS). After 24 h, the concentrations of proinflammatory cytokines in the supernatants of LPS-stimulated cells incubated on P-selectin were <50% of those produced by cells incubated on BSA (interleukin-1beta: P=0.001, tumor necrosis factor-alpha: P=0.004, and interferon-gamma : P=0.026). In contrast, cells incubated on P-selectin produced 74% more of the anti-inflammatory cytokine interleukin-10 than cells incubated on BSA (P=0.013). Neither P-selectin nor BSA stimulated cytokine production in the absence of LPS. Thus, P-selectin modulated the cytokine secretion of peripheral blood mononuclear cells in a coordinated manner that reduced the inflammatory potential of the cells.