12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 10

Diana Vargas¹, C Nascimbene¹, A Lee¹, J Williams², J McArthur¹, C Pardo¹, and Department of Neurology, HIV Neuroscience group
¹Johns Hopkins Univ, Baltimore, MD, USA and ²Bloomberg Sch of Publ Hlth, John Hopkins Univ, Baltimore, MD, USA

BACKGROUND: HIV dementia (HIV+D) is 1 of the most frequent neurological complications associated with AIDS. Neuropathological features of HIV+D include neuroglial activation and in some cases encephalitis. The purpose of this study was to characterize the profile of cytokine and chemokine expression in brain tissues from HIV–D patients as compared with HIV seropositive (HIV+ND) and seronegative controls (HIV–ND) using new protein array techniques.

METHODS: Brain samples from middle frontal gyrus, deep white matter (DEEP WHITE MATTER ) and basal ganglia were obtained at autopsy from HIV+D (n = 10), HIV+ND (n = 10), and HIV–ND (n = 10) patients. A profile of 79 proteins involved in inflammatory pathways such as cytokines, chemokines, and growth and differentiation factors was obtained in all brain regions by cytokine protein array technology. A validation of the cytokine protein array study was carried out by ELISA and immunocytochemical techniques. The magnitude of microglial (MHC class II expression) and astroglial (GFAP) responses was also assessed in all groups for correlation with the protein profiles. Group comparisons were carried out using bootstrap multiple regressions and Mann-Whitney rank sum tests where appropriate.

RESULTS: The basal ganglia appeared to be the main foci of pro-inflammatory activity and showed a significant higher expression of proteins such as MCP-1, MCP-2, MCP-3, MIP-1ß, GRO, and IL-12, (p < 0.0001), while IL-4, MCP-1 (p < 0.0001), and MIF (p < 0.001) were the only set of proteins found to be elevated in the middle frontal gyrus. Interestingly, the deep white matter showed that only IP-10, HGF, and M-CSF as significantly elevated (p < 0.0001). An analysis of the subset of patients with HIV+D with neuropathological evidence of encephalitis showed that IGFBP-2 was significantly elevated (p < 0.05) as compared with patients without encephalitis.

CONCLUSIONS: This study demonstrates that cytokines and chemokines are differentially expressed in brain regions in cases of HIV+D and that the basal ganglia appears to have a prominent pro-inflammatory profile as proteins involved in monocyte/macrophage activation were significantly elevated. This pattern of chemokine increase coincided with a marked increase in the magnitude of microglial activation in the basal ganglia. In HIV+D cases, MCP-1 was the only protein consistently elevated in both middle frontal gyrus and basal ganglia, while the expression of IGFBP-2 appeared to be differentially increased in cases of HIV+D with encephalitis as compared with HIV+D without encephalitis.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.