Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication

Paola Cinque, Luca Vago, Manuela Mengozzi, Valter Torri, Daniela Ceresa, Elisa Vicenzi, Pietro Transidico, Ambrogio Vagani, Silvano Sozzani, Alberto Mantovani, Adriano Lazzarin, Guido Poli

Research output: Contribution to journalArticle

Abstract

Objective: To investigate whether the CC-chemokine monocyte chemotactic protein (MCP)-1 could play a role in the pathogenesis of HIV infection of the central nervous system. This hypothesis was suggested by previous observations, including our finding of elevated cerebrospinal fluid (CSF) levels of this chemokine in patients with cycomegalovirus (CMV) encephalitis. Design and methods: CSF levels of MCP-1 were determined in 37 HIV-infected patients with neurological symptoms, and were compared with both the presence and severity of HIV-1 encephalitis at post-mortem examination and CSF HIV RNA levels. MCP-1 production by monocyte-derived macrophages was tested after in vitro infection of these cells by HIV. Results: CSF MCP-1 levels were significantly higher in patients with (median, 4.99 ng/ml) than in those without (median, 1.72 ng/ml) HIV encephalitis. Elevated CSF MCP-1 concentrations were also found in patients with CMV encephalitis and with concomitant HIV and CMV encephalitis (median, 3.14 and 4.23 ng/ml, respectively). HIV encephalitis was strongly associated with high CSF MCP-1 levels (P = 0.002), which were also correlated to high HIV-1 RNA levels in the CSF (P = 0.007), but not to plasma viraemia. In vitro, productive HIV-1 infection of monocyte-derived macrophages upregulated the secretion of MCP-1. Conclusions: Taken together, these in vivo and in vitro findings support a model whereby HIV encephalitis is sustained by virus replication in microglial cells, a process amplified by recruitment of mononuclear cells via HIV-induced MCP-1.

Original languageEnglish
Pages (from-to)1327-1332
Number of pages6
JournalAIDS (London, England)
Volume12
Issue number11
Publication statusPublished - Jul 30 1998

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Keywords

  • Cellular factors
  • Cerebrospinal fluid
  • Cytokines
  • HIV-1
  • Viral load

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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