ELEVATED CEREBROSPINAL-FLUID LEVELS OF MONOCYTE CHEMOTACTIC PROTEIN-1CORRELATE WITH HIV-1 ENCEPHALITIS AND LOCAL VIRAL REPLICATION

Objective: To investigate whether the CC-chemokine monocyte chemotacti c protein (MCP)-1 could play a role in the pathogenesis of HIV infecti on of the central nervous system. This hypothesis was suggested by pre vious observations, including our finding of elevated cerebrospinal fl uid (CSF) levels oi this chemokine in patients with cytomegalovirus (C MV) encephalitis. Design and methods: CSF levels of MCP-1 were determi ned in 37 HlV-infected patients with neurological symptoms, and were c ompared with both the presence and severity of HIV-1 encephalitis at p ost-mortem examination and CSF HIV RNA levels. MCP-1 production by mon ocyte-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 C MV encephalitis (median, 3.14 and 4.23 ng/ml, respectively). HIV encep halitis 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 infecti on of monocyte-derived macrophages upregulated the secretion of MCP-1. Conclusions: Taken together, these in vivo and in vitro findings supp ort a model whereby HIV encephalitis is sustained by virus replication in microglial cells, a process amplified by recruitment of mononuclea r cells via HIV-induced MCP-1. (C) 1998 Lippincott-Raven Publishers.