Interleukin-6 and granulocyte macrophage-csf in the cerebrospinal fluid from hiv infected subjects with involvement of the central nervous system

Abstract

SUMMARY -We detected the cytokines interleukin-6 (IL-6) and granulocyte macrophage-CSF (GM-CSF) by ELISA in the CSF and serum of 30 HIV-infected patients classified as AIDS dementia complex (ADC), and 20 subjects with other neurological diseases (OND). We have found a high incidence of detectable IL-6 and GM-CSF in the CSF of ADC patients compared with OND patients. No statistical differences were observed between both groups for serum IL-6 and GM-CSF levels. These results suggest an intrathecal synthesis of these cytokines and a possible involvement in the pathogenesis of ADC.KEY WORDS: AIDS dementia complex, cerebrospinal fluid, cytokines (interleukin-6, granulocyte-macrophage-CSF). Interleucina-6 e granulócito-macrófago-CSF no líquido eefalorraquidiano de pacientes infectados por HIV tom comprome t imento do sistema nervoso central.RESUMO -Detectamos as citocinas interleucina-6 (IL-6) e granulócito-macrófago-CSF (GM-CSF) por ELISA no LCR e soro de 30 pacientes infectados por HIV classificados como tendo AIDS-demência complexo (ADC) e de 20 pacientes com outras doenças neurológicas (OND). Encontramos elevada incidência de IL-6 e GM-CSF detectável no LCR de pacientes com ADC, em relação aos pacientes com OND. Diferenças estatísticas não foram observadas entre os dois grupos de pacientes para níveis de IL-6 e GM-CSF no soro. Esses resultados sugerem síntese intratecal dessas citocinas e sua possível participação na patogenia da ADC. PALAVRAS-CHAVE: AIDS-demência complexo, líquido cefalorraquidiano, citocinas (interleucina-6, granulócito-macrófago-CSF).Interleukin-6 (IL-6) and granulocyte-macrophage CSF (GM-CSF) are polypeptide substances produced by monocytes/macrophages and other cell types. IL-6 is a cytokine that promotes differentiation of B-cells to antibody-secreting cells. IL-6 works synergistically with IL-1 to promote B-cell growth, and it has a wide variety of biological activities including mediation of fever and the acute phase response of inflammation 5.The GM-CSF stimulate the production of both granulocytes and macrophages in cultures of human and murine bone marrow cells. Little is known of the pattern of IL-6 and GM-CSF production in human nervous diseases 4. Several studies have suggested a possible role in the pathogenesis of AIDS dementia complex (ADC), but the mechanism of this disease is unclear.In the present study we assayed the IL-6 and GM-CSF in paired cerebrospinal fluid (CSF) and serum from ADC patients, using a sensitive, specific and non-cross reactive ELISA.

Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda

“…Given the link between HIV disease progression and HAND, these increased CSF cytokines and neurodegenerative biomarkers provide insight into the pathophysiology of HAND. Previous studies have demonstrated higher CSF levels of GM-CSF, TNF-α, MMP-1 and MMP-7 in individuals with HIV-associated dementia and encephalitis as compared with individuals without dementia (Perrella, Guerriero et al 1992, Nottet, Persidsky et al 1996, Conant, McArthur et al 1999). …”

Increased In Vivo Activation of Microglia and Astrocytes in the Brains of Mice Transgenic for an Infectious R5 Human Immunodeficiency Virus Type 1 Provirus and for CD4-Specific Expression of Human Cyclin T1 in Response to Stimulation by Lipopolysaccharides

“…Activated astrocytes produce GM-CSF in response to inflammatory signals that would activate microglia, stimulate them to proliferate, and trigger the CNS inflammatory response (41). HIVE is associated with increased GM-CSF production in brains that localized predominantly to astrocytes (15,67), and the AIDS dementia complex is associated with elevated levels of GM-CSF in the cerebrospinal fluid (53). Systemic GM-CSF was reported to induce a 10-fold increase in the HIV load in the spinal fluid of a treated patient (38), and GM-CSF has been reported to increase HIV-1 replication in brain tissue explants (32) and primary monocyte/macrophages and monocyte cell lines (19,37,47,60).…”

Differential ex vivo nitric oxide production by acutely isolated neonatal and adult microglia

“…Both M-CSF and GM-CSF are induced in the CNS in response to inflammation, and a growing body of evidence points to a role for these factors in the pathophysiology of brain disease. These CSFs are elevated in the cerebrospinal fluid of patients with Alzheimer's disease (Tarkowski et al, 2001), multiple sclerosis (Carrieri et al, 1998), HIV-associated dementia (Gallo et al, 1994;Perrella et al, 1992), and acute stroke (Tarkowski et al, 1999), and can be produced by a variety of cells within the CNS, including infiltrating and/or perivascular macrophages.…”