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, 42 (3), 233-40

Increased Production of Inflammatory Cytokines in Mild Cognitive Impairment

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Increased Production of Inflammatory Cytokines in Mild Cognitive Impairment

Shino Magaki et al. Exp Gerontol.

Abstract

Recent studies indicate that chronic inflammation plays a pathogenic role in both the central nervous system (CNS) and periphery in Alzheimer's disease (AD). We have screened for cytokines differentially produced by peripheral blood mononuclear cells (PBMCs) isolated from subjects with mild cognitive impairment (MCI) and mild AD subjects who had progressed from MCI using a commercially available cytokine array. Following determination of expressed cytokines, we quantified levels of the proinflammatory cytokines TNF-alpha, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 using flow cytometry. We have found a significant increase in the levels of IL-6, IL-8, and IL-10 produced by PBMCs stimulated for 24 h with phytohemagglutinin (PHA) in MCI subjects compared to healthy elderly controls. However, in PBMCs stimulated for 48 h with lipopolysaccharide (LPS), lower TNF-alpha/IL-10, IL-6/IL-10, and IL-8/IL-10 ratios were seen in MCI subjects. There were no differences in plasma levels of IL-8 between aged controls, MCI, and mild AD, and the levels of circulating IL-6 and IL-10 were below detection limits. Our data indicate that changes in cytokine production by PBMCs may be detected early in MCI, and an alteration of the immune response may precede clinical AD.

Figures

Fig 1
Fig 1
(A) Alignment of 20 cytokines on the human cytokine array membrane. Abbreviations : GCSF: granulocyte colony stimulating factor; GM-CSF: granulocyte macrophage-colony stimulating factor; IFN: interferon; IL: interleukin; TIMP: tissue inhibitors of metalloproteinase. (B)Representative examples of cytokine array membranes probed with the cell culture supernatants of 48 h LPS stimulated PBMCs from mild AD, MCI, and control. Each dot represents immunoreactive staining for the respective cytokines.
Figure 2
Figure 2
Densitometric quantification of cytokine levels from the cytokine arrays in elderly controls (n=6), MCI (n=4), and mild AD subjects (n=3). To compare results between different membranes, the signals (average density) for each cytokine were normalized to the positive controls on each membrane. Two out of three mild AD cases had detectable levels of IL-10 expression, but only one out of seven control cases showed IL-10 expression. All MCI subjects showed detectable of IL-1β, IL-6, IL-8, and IL-10. Dashed lines indicate the detection limit (0.53), *p < 0.03, significantly different from controls.

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