(Peri)vascular production and action of pro-inflammatory cytokines in brain pathology

Abstract

In response to tissue injury or infection, the peripheral tissue macrophage induces an inflammatory response through the release of IL-1β (interleukin-1β) and TNFα (tumour necrosis factor α). These cytokines stimulate macrophages and endothelial cells to express chemokines and adhesion molecules that attract leucocytes into the peripheral site of injury or infection. The aims of the present review are to (i) discuss the relevance of brain (peri)vascular cells and compartments to bacterial meningitis, HIV-1-associated dementia, multiple sclerosis, ischaemic and traumatic brain injury, and Alzheimer's disease, and (ii) to provide an overview of the production and action of pro-inflammatory cytokines by (peri)vascular cells in these pathologies of the CNS (central nervous system). The brain (peri)vascular compartments are highly relevant to pathologies affecting the CNS, as infections are almost exclusively blood-borne. Insults disrupt blood and energy flow to neurons, and active brain-to-blood transport mechanisms, which are the bottleneck in the clearance of unwanted molecules from the brain. Perivascular macrophages are the most reactive cell type and produce IL-1β and TNFα after infection or injury to the CNS. The main cellular target for IL-1β and TNFα produced in the brain (peri)vascular compartment is the endothelium, where these cytokines induce the expression of adhesion molecules and promote leucocyte infiltration. Whether this and other effects of IL-1 and TNF in the brain (peri)vascular compartments are detrimental or beneficial in neuropathology remains to be shown and requires a clear understanding of the role of these cytokines in both damaging and repair processes in the CNS.