Cerebrospinal fluid and plasma concentrations of proinflammatory mediators in human immunodeficiency virus-infected children

BACKGROUND.The pathogenesis of HIV encephalopathy is poorly understood especially in children. Studies suggest that HIV replication and the release of proinflammatory mediators in the central nervous system contribute to the pathogenesis of HIV dementia in adults. METHODS.Cerebrospinal fluid (CSF) and plasma samples from 23 HIV-infected children were longitudinally analyzed at Weeks 0, 8, 16 and 48 for HIV RNA and concentrations of the following proinflammatory mediatorsmonocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha, regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage-inflammatory protein (MIP)-1-alpha, MIP-1-beta and matrix metalloproteinase-9 (MMP-9). RESULTS.All 23 children had detectable concentrations of MCP-1 in the CSF at all time points evaluated. However, of the remaining of proinflammatory mediators measured in CSF at baseline, only a few children had detectable concentrationstumor necrosis factor-alpha, n = 1; RANTES, n = 5; MMP-9, n = 9; MIP-1-alpha and MIP-1-beta, n = 0. A reduction from baseline to Week 48 was observed in CSF concentrations of MCP-1 and, among children with detectable values, MMP-9, which paralleled declines in CSF HIV RNA. CONCLUSION.These results suggest that MCP-1 and MMP-9 may be involved in the pathogenesis of central nervous system disease in HIV-infected children.