Interleukin-6 is not altered in cerebrospinal fluid of first-degree relatives and patients with Alzheimer's disease

Hampel, Harald; Schoen, D.; Schwarz, Markus J.; Kotter, H. U.; Schneider, Claudia; Sunderland, Trey; Dukoff, Ruth; Levy, Jim; Padberg, Frank; Stübner, Susanne; Buch, Katharina; Müller, Norbert; Möller, Hans‐Jürgen

doi:10.1016/s0304-3940(97)00379-0

Cited by 55 publications

(23 citation statements)

References 21 publications

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“…Likewise, after cell stimulation with LPS, AD patients continued to produce higher levels of IL-1 ␤ , IL-6, IL-10, and TNF-␣ than healthy controls [35] . This is consistent with the hypothesis of the existence of an activated inflammatory state in demented patients; however, some reports presented controversial data regarding increased cytokine levels in blood and cerebrospinal fluid of AD patients [36][37][38] .…”

Section: Discussionsupporting

confidence: 87%

Peripheral Inflammatory Cytokines as Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment

Guerreiro¹,

Santana²,

Brás³

et al. 2007

Neurodegener Dis

133

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Background: Several lines of evidence in the literature have shown that inflammation is involved in the pathogenesis of Alzheimer’s disease (AD). However, the results from the evaluation of serum inflammatory markers in AD patients have been controversial. Objective: To determine if any differences exist in the monocytic secretion pattern of IL-1β, IL-6, IL-12 and TNF-α from mild cognitive impairment (MCI) and AD patients, when compared with healthy age-matched controls. Methods: To evaluate the percentage of peripheral monocytes secreting IL-1β, IL-6, IL-12 and TNF-α along with the relative levels of these proteins, a cytofluorimetric analysis was conducted under basal conditions and after lipopolysaccharide-induced cell activation. Results: We found, in AD and MCI patients, a significant raise in the percentage of monocytes producing the studied cytokines (under basal conditions and after the exposure to an inflammatory stimulus), as well as a decreased competence of these cells to respond to inflammatory challenges, when compared with controls. Conclusions: These results agree with a persistent inflammatory status in AD, reinforcing the hypothesis of a progressive impairment of the immune response in this disorder and suggesting that monocytes may be good targets to study the progression from MCI to AD.

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Section: Discussionsupporting

confidence: 87%

Peripheral Inflammatory Cytokines as Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment

Guerreiro¹,

Santana²,

Brás³

et al. 2007

Neurodegener Dis

133

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“…IL-6 levels were determined using solid phase Quantikine human immunoassay kits (R&D Systems) according to the manufacturer's instructions, as described in our previous research (Hampel et al, 1997;Padberg et al, 1999). Sensitivities for undiluted samples were 0.094 pg/ml.…”

Section: Assays Of Inflammatory Mediatorsmentioning

confidence: 99%

Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro

Lue

Rydel

Brigham

et al. 2001

Glia

Self Cite

353

232

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We have previously developed and characterized isolated microglia and astrocyte cultures from rapid (<4 h) brain autopsies of Alzheimer's disease (AD) and nondemented elderly control (ND) patients. In the present study, we evaluate the inflammatory repertoire of AD and ND microglia cultured from white matter (corpus callosum) and gray matter (superior frontal gyrus) with respect to three major proinflammatory cytokines, three chemokines, a classical pathway complement component, a scavenger cell growth factor, and a reactive nitrogen intermediate. Significant, dose-dependent increases in the production of pro-interleukin-1beta (pro-IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory peptide-1alpha (MIP-1alpha), IL-8, and macrophage colony-stimulating factor (M-CSF) were observed after exposure to pre-aggregated amyloid beta peptide (1-42) (Abeta1-42). Across constitutive and Abeta-stimulated conditions, secretion of complement component C1q, a reactive nitrogen intermediate, and M-CSF was significantly higher in AD compared with ND microglia. Taken together with previous in situ hybridization findings, these results demonstrate unequivocally that elderly human microglia provide a brain endogenous source for a wide range of inflammatory mediators.

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“…The reactive glial cells produce cytokines such as interleukin-1 (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) (Griffin et al, 1989;Bauer et al, 1991;Dickson et al, 1993), as well as chemokines, complement factors and acute phase reactants (Vandenabeele and Fiers, 1991;Eikelenboom et al, 1994;Neuroinflammation working group, 2000;Galimberti et al, 2003;McGeer and McGeer, 2003). Furthermore, elevated levels of IL-1β (Cacabelos et al, 1991;Blum-Degen et al, 1995), TNF-α (Tarkowski et al, 1999) and chemokines (Galimberti et al, 2003), have been observed in serum and cerebrospinal fluid (CSF) from AD-patients, whereas the levels of IL-6 have been shown to be either increased or unaltered as compared to healthy, age-matched controls (BlumDegen et al, 1995;Hampel et al, 1997;Martinez et al, 2000;Neuroinflammation working group, 2000). Significant activation of microglia appears to occur at an early stage of the disease, i.e., before severe cognitive decline has occurred (Vehmas et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Cytokine production by a human microglial cell line: Effects of ßamyloid and α-melanocyte-stimulating hormone

et al. 2005

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Senile plaques in the Alzheimer's disease (AD) are formed by aggregation of beta-amyloid (Abeta) peptide. Abeta peptide has been shown to activate microglia and stimulate their production of inflammatory factors, such as cytokines. In the AD brain, the continued presence of amyloid plaques may keep microglia persistently activated, leading to chronic inflammation in the CNS. It is well established that alpha-melanocyte-stimulating hormone (alpha-MSH) gives rise to anti-inflammatory and anti-pyretic effects. The biological activities of alpha-MSH are mediated by one or more of the melanocortin receptor (MCR) subtypes, i.e. MCR1 - MCR5. The aim of the present study was to determine the effect of alpha-MSH alone and on Abeta-activated microglial cells with regard to the secretion of inflammatory cytokines, such as interleukin-6 (IL-6), and to determine which receptor subtype mediates the effects of alpha-MSH. The human microglial cell line, CHME3, was incubated for 24 h with freshly dissolved Abeta(1-40), interferon-gamma (IFN-gamma) and/or alpha-MSH. Freshly dissolved Abeta(1-40) (5-60 microM) resulted in a dose-dependent decrease in cell viability, along with a dose-dependent increase in IL-6 release. Neither IFN-gamma nor alpha-MSH affected the Abeta-induced secretion of IL-6, but resulted in a dose-dependent increase in basal IL-6 release. Agouti, the endogenous antagonist of MCR1 and 4, further increased the alpha-MSH-induced secretion of IL-6. RT-PCR showed the expression of MCR1, MCR3, MCR4 and MCR5 mRNA. The combined data suggest that the effect of alpha-MSH in increasing IL-6 release from the human microglial cell line is mediated by MCR3 or MCR5.

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Interleukin-6 is not altered in cerebrospinal fluid of first-degree relatives and patients with Alzheimer's disease

Cited by 55 publications

References 21 publications

Peripheral Inflammatory Cytokines as Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment

Peripheral Inflammatory Cytokines as Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment

Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro

Cytokine production by a human microglial cell line: Effects of ßamyloid and α-melanocyte-stimulating hormone

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