Inflammatory mediators and the blood-brain barrier

Inflammation in the central nervous system (CNS) is characterized by a complex series of events that involve several types of cells and a large number of interacting, biologically active molecules collectively called inflammatory mediators. Due to their position at the blood-brain interface, cerebral endothelial cells (EC) are exposed to circulating inflammatory mediators released peripherally by immune cells and locally by infiltrating inflammatory cells and CNS resident cells, including astrocytes and microglia. In addition, upon stimulation brain EC synthesize and release their own set of inflammatory mediators, mainly chemokines, cytokines, growth factors and prostaglandins. Inflammatory mediators induce profound changes on the phenotype, function and permeability properties of the endothelium, which, in turn plays key roles in the initiation, progression and regulation of immune responses. The aim of this chapter is to provide a comprehensive review of the function and mechanisms of action of key cytokines and “classical” inflammatory mediators at the BBB, including those produced by cerebral EC cells. The expression and function of chemokines at the BBB are discussed in Chapter 11.