CHEMOKINES AND RECEPTORS IN HIV ENCEPHALITIS

Background: Chemokines are involved in the migration of leukocytes and have been implicated in several inflammatory diseases of the central nervous system. Some of their receptors have been proposed to mediate HIV infection. Objective: To determine changes in chemokine and recept or expression in HIV encephalitis, and to determine whether upregulati on leads to recruitment of infected monocytes across the blood-brain b arrier and participates in HIV neuropathology. Methods: Immunocytochem istry and double-label immunofluorescent laser confocal microscopy was performed with antibodies to chemokines and their receptors on brain tissues from patients who died with or without HIV encephalitis. In vi vo distribution was compared with in vitro cultures of human neuroglia l cells. Results: The beta-chemokines monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha, and RANTES were detected on b rain macrophages. Their presence was associated with the histopatholog ical signs of HIV encephalitis. The alpha-chemokines IP-10 (10 kDa inf lammatory protein) and interleukin-8 were expressed by astrocytes in a ll tissues, including controls. Presence of the CXC-chemokine receptor (CXCR)-4 was seen on brain macrophages/microglia, neurons, and astroc ytes. CC-Chemokine receptor (CCR)-5 was detected only on macrophages/m icroglia. CCR-3 and CCR-1 were expressed by macrophages and endothelia l cells. In vitro studies examining the presence of CCR-3, CCR-5, and CXCR-4 on human brain cell cultures demonstrated abundant neuronal and microglial expression. Conclusions: Expression of a variety of chemok ines and receptors was shown to be increased in HIV encephalitis brain tissues particularly in areas of neuroglial reaction. The expression pattern supported their involvement in the recruitment of inflammatory infiltrates and formation of microglial nodules. Presence of chemokin e receptors on neurons may be involved in the pathogenesis of neurolog ic damage in AIDS patients. (C) 1998 Lippincott-Raven Publishers.