Elevated cerebrospinal fluid levels of monocyte chemotactic ... : AIDS (original) (raw)

ARTICLE

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

Cinque, Paola1,8; Vago, Luca2; Mengozzi, Manuela3; Torri, Valter4; Ceresa, Daniela1; Vicenzi, Elisa3; Transidico, Pietro5; Vagani, Ambrogio6; Sozzani, Silvano5; Mantovani, Alberto5,7; Lazzarin, Adriano1; Poli, Guido2

1Division of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy

2Institute of Pathology, ‘Luigi Sacco’ Hospital, Milan, Italy

3AIDS Immunopathogenesis Unit, P2/P3 Laboratories, San Raffaele Scientific Institute, Milan, Italy

4Biometric Unit, Department of Oncology, ‘Mario Negri’ Institute for Pharmacological Research, Milan, Italy

5Department of Immunology and Cell Biology, ‘Mario Negri’ Institute for Pharmacological Research, Milan, Italy

6Institute of Pathology, San Raffaele Scientific Institute, Milan, Italy

7Department of Biotechnology, Section of General Pathology, University of Brescia, Brescia, Italy.

8Requests for reprints to: Dr Paola Cinque, Division of Infectious Diseases, San Raffaele Hospital, Via Stamira d'Ancona 20, 20127 Milano, Italy.

Sponsorship: Supported by the Istituto Superiore di Sanità, Italy.

Date of receipt: 24 February 1998; revised: 27 March 1998; accepted: 2 April 1998.

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 cytomegalovirus (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.