title: Protein changes in CSF of HIV-infected patients: evidence for loss of neuroprotection.
abstract: To begin to unravel the complexity of HIV-associated changes in the brain, broader, multifaceted analyses of cerebrospinal fluid (CSF) are needed that examine a wide range of proteins reflecting different functions. To provide the first broad profiles of protein changes in the CSF of HIV-infected patients, we used antibody arrays to measure 120 cytokines, chemokines, growth factors, and other proteins. CSF from HIV-infected patients with a range of cognitive deficits was compared to CSF from uninfected, cognitively normal patients to begin to identify protein changes associated with HIV infection and neurological disease progression. Uninfected patients showed relatively consistent patterns of protein expression. Highly expressed proteins in CSF included monocyte chemotactic protein-1, tissue inhibitors of metalloproteases, granulocyte colony-stimulating factor, adiponectin, soluble tumor necrosis factor receptor-1, urokinase-type plasminogen activator receptor, and insulin-like growth factor binding protein-2. Inflammatory and anti-inflammatory cytokines were expressed at low levels. HIV-infected patients showed increases in inflammatory proteins (interferon-gamma, tumor necrosis factor-alpha), anti-inflammatory proteins (IL-13), and chemokines but these correlated poorly with neurological status. The strongest correlation with increasing severity of neurological disease was a decline in growth factors, particularly, brain-derived neurotrophic factor and NT-3. These studies illustrate that HIV infection is associated with parallel changes in both inflammatory and neuroprotective proteins in the CSF. The inverse relationship between growth factors and neurological disease severity suggests that a loss of growth factor neuroprotection may contribute to the development of neural damage and may provide useful markers of disease progression.
authors.affiliation: Department of Neurology, University of North Carolina, CB #7025, 6113 Neuroscience Research Bldg, 115 Mason Farm Road, Chapel Hill, NC 27599, USA. meekerr@neurology.unc.edu
authors.forename: Rick B
authors.initials: RB
authors.lastname: Meeker
authors.forename: Winona
authors.initials: W
authors.lastname: Poulton
authors.forename: Silva
authors.initials: S
authors.lastname: Markovic-Plese
authors.forename: Colin
authors.initials: C
authors.lastname: Hall
authors.forename: Kevin
authors.initials: K
authors.lastname: Robertson
mesh_terms: D001921:Brain / Q000473:pathology / Q000821:virology; D019208:Brain-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000209:etiology / Q000523:psychology* / Q000821:virology; D016207:Cytokines / Q000134:cerebrospinal fluid*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000134:cerebrospinal fluid; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000473:pathology / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000134:cerebrospinal fluid*; D009483:Neuropsychological Tests; D020933:Neurotrophin 3 / Q000134:cerebrospinal fluid*; D040081:Protein Array Analysis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000134:cerebrospinal fluid; D012720:Severity of Illness Index; D014568:Urokinase-Type Plasminogen Activator / Q000134:cerebrospinal fluid
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D047888:Receptors, Tumor Necrosis Factor, Type I; D016179:Granulocyte Colony-Stimulating Factor; D014568:Urokinase-Type Plasminogen Activator