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Background:  Chemokine receptor CCR2 and its ligand MCP-1 (monocyte chemoattractant protein-1)/CCL2 are involved in the recruitment of inflammatory cells to the central nervous system in infectious conditions of the nervous system. We examined the concentration of MCP-1 in cerebrospinal fluid (CSF) and the expression of CCR2 on monocytes in CSF of HIV-infected patients on ART, including protease-inhibitors (PI) and patients off ART.

Methods:  We used 6-color flow cytometry to identify percentages of CCR2⁺ monocytes in paired CSF and blood samples. Monocytes were identified using the markers CD14 and CD4^low. CCR2 expression was determined using a FMO (fluorescence minus one) sample. MCP-1 in CSF was measured using a MCP-1-ELISA kit.

Results:  CCR2 expression was increased on CSF monocytes compared to blood monocytes in all 28 HIV-infected patients and 2 uninfected controls (p < 0.0001). The mean percentage of CCR2⁺ monocytes among CD14⁺/CD4^low monocytes in CSF was 6.37 ± 6.34% and in blood 0.35 ± 0.25%. Of 28 HIV-infected patients, 16 were on ART, 7 on PI, 12 were off ART. The mean level of MCP-1 in CSF was highest in patients off ART (637.8 ± 169.8 pg/mL), lower in patients failing therapy (509.6 ± 164.4) and similar in successes and in uninfected controls (429.1 ± 136.0 and 431.3 ± 44.48, respectively). In HIV-infected patients, plasma viral load correlated with MCP-1 in CSF (p = 0.016, r² = 0.22). In patients on ART, CCR2 expression on monocytes in CSF and blood correlated with MCP-1 in CSF (p = 0.0057, r² = 0.43). In patients off ART, CCR2 expression on monocytes in CSF correlated with the CSF/plasma albumin ratio (p = 0.026, r² = 0.44).

Conclusions:  These observations are consistent with a role for CCR2 and its ligand MCP-1/CCL2 in trafficking of monocytes into CSF of HIV-infected patients on and off ART including PI. Increased permeability of the blood–brain barrier in viremic patients may contribute to enrichment of CCR2⁺ monocytes in CSF of untreated patients. The majority of monocytes in CSF are CCR2^–, suggesting that other chemokine receptors may be involved or that CCR2 expression is down-regulated. 

Keywords: Monocyte Chemoattractant Protein-1 (MCP-1); chemokine receptor CCR2; cerebrospinal fluid