The role of cytokines in regulating platelet-activating factor (PAF) synthesis in endothelial cells

Asthma is a disease of the airways in which an inappropriate inflammatory response occurs. It is characterized by the expression of Th2 type cytokines such as IL-4. PAF is a potent phospholipid autocoid that participates in leukocyte recruitment during inflammation. Human umbilical vein endothelial cells (HUVEC) synthesize and express PAF in response to several agonists including histamine and thrombin. In this study we examined the role of cytokines in regulating PAF synthesis. HUVEC were first treated for 24 hr with IL-4 and then stimulated for 5 min with histamine or thrombin. IL-4 stimulation primed HUVEC for increased PAF production in response to either histamine or thrombin. IL-4 also increased the sensitivity of HUVEC to histamine. We conclude that the increase in histamine sensitivity seen in IL-4 treated HUVEC is due, in part, to an increase in histamine receptors. We were unable to define the mechanism behind increased histamine or thrombin-induced PAF synthesis in IL-4 treated HUVEC.