Increased intrathecal release of soluble fractalkine in HIV-infected patients

The CX3C 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 5 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.