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Decreased IL-8 levels in CSF and serum of AD patients and negative correlation of MMSE and IL-1 β

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ABSTRACT

Background: It is widely accepted that neuroinflammatory processes play an important role in the pathogenesis of Alzheimer’s disease (AD) and high levels of cytokines and chemokines are detected around Aβ plaques.

Methods: As neuroinflammation is involved in the development and progression of AD, we measured the pro-inflammatory cytokines interleukin 1β (IL-1β), IL-8 and tumor necrosis factor α (TNF-α) in serum and cerebrospinal fluid (CSF) samples from 45 AD patients and 53 age-matched control subjects using a highly sensitive multiplex electrochemiluminescence assay. To address the association with disease progression we correlated cognitive status with cytokine levels.

Results: CSF as well as serum IL-8 levels were found to be significantly lower in AD patients than in controls (p = 0.02). A statistically significant inverse correlation was observed between the CSF level of IL-1β and the MMSE score (rs = -0.03, p = 0.02). We therefore stratified the AD patients by their MMSE scores into three equal groups and found that in the AD group with the most severe cognitive impairment CSF-IL-1β was significantly increased compared to age-matched controls (p < 0.05), whereas in the other investigated groups the increase was not statistically significant.

Conclusion: Our results confirm data suggesting that cytokine alterations are involved in AD pathogenesis and may be helpful as a biomarker for monitoring disease progression.

Electronic supplementary material: The online version of this article (doi:10.1186/s12883-016-0707-z) contains supplementary material, which is available to authorized users.

No MeSH data available.


Cytokine levels in CSF samples of AD patients compared to controls. Box plots comparing CSF IL-1β, IL-8 and TNF-α levels between AD patients and age-matched controls. a IL-1β levels were not altered in AD patients compared to controls (p = 0.12). b IL-8 levels, by comparison, were significantly reduced in AD patients (p = 0.02). c TNF-α showed no significant difference (p = 0.83). Dark horizontal lines represent the mean, with the box representing the 25th and 75th percentiles of the observed data, the whiskers representing the 5th and 95th percentiles, and outliers represented by dots. P values were calculated using the Mann-Whitney Rank sum test
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Fig1: Cytokine levels in CSF samples of AD patients compared to controls. Box plots comparing CSF IL-1β, IL-8 and TNF-α levels between AD patients and age-matched controls. a IL-1β levels were not altered in AD patients compared to controls (p = 0.12). b IL-8 levels, by comparison, were significantly reduced in AD patients (p = 0.02). c TNF-α showed no significant difference (p = 0.83). Dark horizontal lines represent the mean, with the box representing the 25th and 75th percentiles of the observed data, the whiskers representing the 5th and 95th percentiles, and outliers represented by dots. P values were calculated using the Mann-Whitney Rank sum test

Mentions: In our study cohort, the CSF IL-1β levels of AD patients (0.54 / 0.27–0.82 pg/ml) showed no change compared to non-demented elderly control subjects (0.33 / 0.24–0.53 pg/ml; p = 0.12) (Fig. 1a). IL-8 levels were found to be significantly lower in AD patients than in controls (AD: 35.0 / 29.67–46.16 pg/ml, control: 41.73 / 36.73–58.74 pg/ml; p = 0.02) (Fig. 1b). In the case of TNF-α, its level in CSF was not changed in AD samples (0.42 / 0.30–0.64 pg/ml) compared to control subjects (0.51 / 0.29–0.70 pg/ml; p = 0.83) (Fig. 1c). As depression frequently occurs already in early stages of AD and IL-8 is discussed to be involved in depressive disorders, we included subjects suffering from depression in our control cohort as well. We compared CSF IL-8 levels of control subjects suffering from a depression (39.10 / 35.71–54.84 pg/ml) with CSF IL-8 levels of non-depressed control subjects (44.01 / 35.94–67.43 pg/ml). We did not see a statistically significant difference (p = 0.71) (Additional file 1: Figure S1A). Further we omitted the depressed control subjects (44.01 / 35.94–67.43 pg/ml) and compared CSF IL-8 levels with these of AD patients (35.90 / 29.67–46.16 pg/ml) and observed the same difference as when the depressed control subjects were included (p = 0.03) (Additional file 1: Figure S1C).Fig. 1


Decreased IL-8 levels in CSF and serum of AD patients and negative correlation of MMSE and IL-1 β
Cytokine levels in CSF samples of AD patients compared to controls. Box plots comparing CSF IL-1β, IL-8 and TNF-α levels between AD patients and age-matched controls. a IL-1β levels were not altered in AD patients compared to controls (p = 0.12). b IL-8 levels, by comparison, were significantly reduced in AD patients (p = 0.02). c TNF-α showed no significant difference (p = 0.83). Dark horizontal lines represent the mean, with the box representing the 25th and 75th percentiles of the observed data, the whiskers representing the 5th and 95th percentiles, and outliers represented by dots. P values were calculated using the Mann-Whitney Rank sum test
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037590&req=5

Fig1: Cytokine levels in CSF samples of AD patients compared to controls. Box plots comparing CSF IL-1β, IL-8 and TNF-α levels between AD patients and age-matched controls. a IL-1β levels were not altered in AD patients compared to controls (p = 0.12). b IL-8 levels, by comparison, were significantly reduced in AD patients (p = 0.02). c TNF-α showed no significant difference (p = 0.83). Dark horizontal lines represent the mean, with the box representing the 25th and 75th percentiles of the observed data, the whiskers representing the 5th and 95th percentiles, and outliers represented by dots. P values were calculated using the Mann-Whitney Rank sum test
Mentions: In our study cohort, the CSF IL-1β levels of AD patients (0.54 / 0.27–0.82 pg/ml) showed no change compared to non-demented elderly control subjects (0.33 / 0.24–0.53 pg/ml; p = 0.12) (Fig. 1a). IL-8 levels were found to be significantly lower in AD patients than in controls (AD: 35.0 / 29.67–46.16 pg/ml, control: 41.73 / 36.73–58.74 pg/ml; p = 0.02) (Fig. 1b). In the case of TNF-α, its level in CSF was not changed in AD samples (0.42 / 0.30–0.64 pg/ml) compared to control subjects (0.51 / 0.29–0.70 pg/ml; p = 0.83) (Fig. 1c). As depression frequently occurs already in early stages of AD and IL-8 is discussed to be involved in depressive disorders, we included subjects suffering from depression in our control cohort as well. We compared CSF IL-8 levels of control subjects suffering from a depression (39.10 / 35.71–54.84 pg/ml) with CSF IL-8 levels of non-depressed control subjects (44.01 / 35.94–67.43 pg/ml). We did not see a statistically significant difference (p = 0.71) (Additional file 1: Figure S1A). Further we omitted the depressed control subjects (44.01 / 35.94–67.43 pg/ml) and compared CSF IL-8 levels with these of AD patients (35.90 / 29.67–46.16 pg/ml) and observed the same difference as when the depressed control subjects were included (p = 0.03) (Additional file 1: Figure S1C).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: It is widely accepted that neuroinflammatory processes play an important role in the pathogenesis of Alzheimer’s disease (AD) and high levels of cytokines and chemokines are detected around Aβ plaques.

Methods: As neuroinflammation is involved in the development and progression of AD, we measured the pro-inflammatory cytokines interleukin 1β (IL-1β), IL-8 and tumor necrosis factor α (TNF-α) in serum and cerebrospinal fluid (CSF) samples from 45 AD patients and 53 age-matched control subjects using a highly sensitive multiplex electrochemiluminescence assay. To address the association with disease progression we correlated cognitive status with cytokine levels.

Results: CSF as well as serum IL-8 levels were found to be significantly lower in AD patients than in controls (p = 0.02). A statistically significant inverse correlation was observed between the CSF level of IL-1β and the MMSE score (rs = -0.03, p = 0.02). We therefore stratified the AD patients by their MMSE scores into three equal groups and found that in the AD group with the most severe cognitive impairment CSF-IL-1β was significantly increased compared to age-matched controls (p < 0.05), whereas in the other investigated groups the increase was not statistically significant.

Conclusion: Our results confirm data suggesting that cytokine alterations are involved in AD pathogenesis and may be helpful as a biomarker for monitoring disease progression.

Electronic supplementary material: The online version of this article (doi:10.1186/s12883-016-0707-z) contains supplementary material, which is available to authorized users.

No MeSH data available.