Measurement of soluble inflammatory mediators in cerebrospinal fluid of human immunodeficiency virus-positive patients at distinct stages of infection by solid-phase protein array
The objective of this study was to evaluate immune cytokine expression in cerebrospinal fluid (CSF) of patients with human immunodeficiency virus-1 (HIV-1)-associated dementia (HAD) using a novel cytokine array assay. HIV-1 induces a condition resembling classical subcortical dementia, known as HAD. The immune mechanisms contributing to HAD have not been elucidated. Cytokine expression in CSF was determined by solid-phase protein array in 33 neurologically asymptomatic HIV-positive male patients and were compared to levels in non-HIV controls and patients with HAD. Neurological examinations and lumbar and venous punctures were conducted in all patients and controls. Interleukin (IL)-1, IL-4, and IL-10, were up-regulated in all treated acquired immunodeficiency syndrome (AIDS) patients independent of neurological status compared to controls. In contrast, interferon gamma (IFN-γ), IL-1α, IL-15, and tumor necrosis factor alpha (TNF-α) were highly expressed in patients with HAD compared to undemented HIV-positive patients. These results show that solid-phase protein array can detect immunological changes in patients infected with HIV. Cytokine expression levels differ in different disease stages and in patients on different treatment paradigms. Pending further validation on a larger number of patients, this method may be a useful tool in CSF diagnostics and the longitudinal evaluation of patient with HAD.
Keywordschemokine cytokine HIV neuro-AIDS protein array
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- Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007). Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69: 1789–1799.CrossRefPubMedGoogle Scholar
- Arendt G, Nolting T, Frisch C, Husstedt IW, Gregor N, Koutsilieri E, Maschke M, Angerer A, Obermann M, Neuen-Jacob E, Adams O, Loeffert S, Riederer P, ter Meulen V, Sopper S (2007). Intrathecal viral replication and cerebral deficits in different stages of human immunodeficiency virus disease. J NeuroVirol 13: 225–232.CrossRefPubMedGoogle Scholar
- Buch S, Pinson D, King CL, Raghavan R, Hou Y, Li Z, Adany I, Hicks A, Villinger F, Kumar A, Narayan O (2001). Inhibitory and enhancing effects of IFN-gamma and IL-4 on SHIV(KU) replication in rhesus macaque macrophages: correlation between Th2 cytokines and productive infection in tissue macrophages during late-stage infection. Cytokine 13: 295–304.CrossRefPubMedGoogle Scholar
- Cysique LA, Maruff P, Brew BJ (2004). Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J NeuroVirol 10: 350–357.CrossRefPubMedGoogle Scholar
- Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, Thompson MA, Carpenter CC, Fischl MA, Gazzard BG, Gatell JM, Hirsch MS, Katzenstein DA, Richman DD, Vella S, Yeni PG, Volberding PA (2006). Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA 296: 827–843.CrossRefPubMedGoogle Scholar
- Killebrew DA, Troelstrup D, Valcour V, Williams A, Aguon J, Sapalo D, Shikuma C, Ratto-Kim S, Shiramizu B (2005). Discordant plasma and cerebral spinal fluid cytokines/chemokines in relation to HIV-1-associated dementia. Cell Mol Biol (Noisy-le-grand) 51(Suppl): OL745-OL754.Google Scholar
- Malaspina A, Moir S, Ho J, Wang W, Howell ML, O’Shea MA, Roby GA, Rehm CA, Mican JM, Chun TW, Fauci AS (2006). Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: correlation with increased IL-7. Proc Natl Acad Sci U S A 103: 2262–227.CrossRefPubMedGoogle Scholar
- Marchetti G, Gori A, Casabianca A, Magnani M, Franzetti F, Clerici M, Perno CF, Monforte A, Galli M, Meroni L (2006). Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART. AIDS 20: 1727–1736.CrossRefPubMedGoogle Scholar
- Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW (2006). A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354: 899–910.CrossRefPubMedGoogle Scholar
- Tong N, Perry SW, Zhang Q, James HJ, Guo H, Brooks A, Bal H, Kinnear SA, Fine S, Epstein LG, Dairaghi D, Schall TJ, Gendelman HE, Dewhurst S, Sharer LR, Gelbard HA (2000). Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system. J Immunol 164: 1333–1339.PubMedGoogle Scholar
- Wahl SM, Allen JB, McCartney-Francis N, Morganti-Kossmann MC, Kossmann T, Ellingsworth L, Mai UE, Mergenhagen SE, Orenstein JM (1991). Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. J Exp Med 173: 981–991.CrossRefPubMedGoogle Scholar