title: Tumour necrosis factor-alpha mediates blood-brain barrier damage in HIV-1 infection of the central nervous system.
abstract: The pathogenesis of brain inflammation and damage by human immunodeficiency virus (HIV) infection is unclear. Because blood-brain barrier damage and impaired cerebral perfusion are common features of HIV-1 infection, we evaluated the role of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in mediating disruption of the blood-brain barrier. Levels of TNF-alpha were more elevated in cerebrospinal fluid (CSF) than in serum of HIV-1 infected patients and were mainly detected in those patients who had neurologic involvement. Intrathecal TNF-alpha levels correlated with signs of blood-brain barrier damage, manifested by high CSF to serum albumin quotient, and with the degree of barrier impairment. In contrast, intrathecal IL-1beta levels did not correlate with blood-brain barrier damage in HIV-1 infected patients. TNF-alpha seems to be related to active neural inflammation and to blood-brain barrier damage. The proinflammatory effects of TNF-alpha in the nervous system are dissociated from those of IL-1beta.
authors.affiliation: Department of Neurochemistry Institute of Neurology The National Hospital for Neurology and Neurosurgery Queen Square London WC1N 3BG UK.
authors.forename: M K
authors.initials: MK
authors.lastname: Sharief
authors.forename: M
authors.initials: M
authors.lastname: Ciardi
authors.forename: E J
authors.initials: EJ
authors.lastname: Thompson
authors.forename: F
authors.initials: F
authors.lastname: Sorice
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: V
authors.initials: V
authors.lastname: Vullo
authors.forename: A
authors.initials: A
authors.lastname: Cirelli