Increased Intrathecal Release of Soluble Fractalkine in HIV-Infected Patients

Abstract

The CX(3)C chemokine fractalkine is suggested to play an important role in inflammatory brain diseases, for example, because of its chemotactic properties. To investigate the release of soluble fractalkine in HIV-induced brain diseases fractalkine levels were determined in cerebrospinal fluid (CSF) and serum samples of HIV-infected patients with (n = 10) and without (n = 23) HIV-induced CNS complications, using semiquantitative Western blot analysis. Fractalkine CSF levels were significantly elevated (p < 0.05) in HIV-infected patients with CNS diseases compared with those without, and compared with HIV-negative controls (n = 23). Fractalkine serum concentrations did not differ between the two groups of HIV-infected patients, but were significantly elevated (p < 0.05) in HIV-infected patients with CNS complications compared with HIV-negative controls. Levels of fractalkine did not correlate with the CSF and serum HIV load and other CSF parameters. In one patient with HIV-associated dementia and myelopathy CSF fractalkine levels decreased on initiation of antiretroviral therapy and subsequent clinical improvement. In conclusion, intrathecal fractalkine release was observed in the majority of patients with HIV infection. The highest levels of soluble fractalkine were detected in CSF (and serum) samples of patients with HIV-induced CNS disorders. These results suggest a dysregulation of brain soluble fractalkine release during HIV infection.

Factor Analysis of Proton MR Spectroscopic Imaging Data in HIV Infection: Metabolite-derived Factors Help Identify Infection and Dementia

“…Mohamed et al dementia-related literature (31)(32)(33)(34). CD4+ T-cell depletion was related to increased HIV RNA levels in the blood ( R S = 2 0.51, P , .00001), but correlation was lacking with respect to viral levels in the CSF ( R S = 0.29, P , .03; Bonferroni correction: P , .0009).…”

A guide to interpretation of neuroimmunological biomarkers in the combined antiretroviral therapy-era of HIV central nervous system disease

“…98 Two studies have demonstrated nonspecific elevations in CSF fractalkine in HIV-positive patients with neurological sequelae including dementia. 99,100 This is not immediately reconciled with in vitro data suggesting fractalkine is neuroprotective. Elevated levels may suggest a host attempt at neuroprotection.…”

Chemokines and Their Receptors in Central Nervous System Disease

“…Several studies showed elevated levels of CX3CL1 in the CSF of patients with HAD compared to controls (healthy individuals, AIDS patients without HAD) and a function of CX3CL1 in HAD was accordingly suggested [123][124][125]. Since an increase of CX3CL1 in CSF was not only found in HAD patients but also under other neurodegenerative conditions, this chemokine might be a general marker for neurodegeneration [126,127].…”

“…Since CX3CL1 is expressed in neurons and released from these cells under stress conditions [131,132] and since microglia express the corresponding chemokine receptor CX3CR1, a role of CX3CL1 in neuron-microglia signaling has been suggested [123][124][125][130][131][132][133]. Indeed, in various models of neurodegeneration and/or neuroinflammation an increase in (neurotoxic)-microglia activity was found when CX3CL1-CX3CR1 signaling was absent [130].…”