Interleukin-1β/Interleukin10 Ratio Produced by Monocytes as a Biomarker of Neuroinflammation in Autism

Jyonouchi, Harumi; Geng, Lee; Buyske, Steven

doi:10.4172/2155-9899.1000503

Cited by 5 publications

(20 citation statements)

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“…1 . Fluctuating IL-1ß/IL-10 ratios in ASD PBMo were observed in some ASD subjects, a finding that is consistent with our previous study [ 25 ]. It should be noted that in selected ASD subjects ( N = 23), PBMo samples were obtained 2–3 times.…”

Section: Resultssupporting

confidence: 93%

“…This is due to the fact that we have previously observed changes in cytokine production by ASD PBMo in association with changes in behavioral symptoms [ 9 ]. Non-ASD control cells revealed the similar tight ranges of IL-1ß/IL-10 ratios, as we have reported before [ 25 ]. Thus, ASD monocyte samples examined in this study revealed a much higher frequency of high/low IL-1ß/IL-10 ratios that were either higher or lower than non-ASD control cells ( p < 0.0005 by Fisher’s exact test).…”

Section: Resultssupporting

confidence: 84%

“…Previously, we have observed marked variation in the production of IL-1ß and IL-10 by PBMo in a subset of ASD subjects [ 9 ]. These changes are more easily appreciated when expressed as IL-1ß/IL-10 ratios, in parallel with changes in behavioral symptoms [ 25 ]. In this study, we examined IL-1ß/IL-10 ratios produced by the ASD PBMo in comparison with non-ASD PBMo, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, ASD monocyte samples examined in this study revealed a much higher frequency of high/low IL-1ß/IL-10 ratios that were either higher or lower than non-ASD control cells ( p < 0.0005 by Fisher’s exact test). Therefore, we subdivided the ASD PBMo samples into high, normal, and low IL-1ß/IL-10 ratio groups, defining as described below [ 25 ]:

Fig. 1 IL-1β/IL-10 ratios under cultures without a stimulus and with stimuli (LPS, zymosan, CL097, and β-lactam).…”

Section: Resultsmentioning

confidence: 99%

“…We have reported before that certain ASD subjects revealed high or low IL-1ß/IL-10 ratios, depending on the time points when the sample was obtained, while others’ IL-1ß/IL-10 ratios remained stable [ 25 ]. The ASD subjects whose IL-1ß/IL-10 ratios remained stable generally fell into the group with normal IL-1ß/IL-10 ratios in our previous observation.…”

Section: Resultsmentioning

confidence: 99%

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MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study)

Jyonouchi

Geng

Streck

et al. 2017

J Neuroinflammation

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BackgroundMicroRNAs (miRNAs) play a major role in regulating immune responses at post-transcriptional levels. Previously, we have reported fluctuating interlukine-1ß (IL-1ß)/IL-10 ratios produced by peripheral blood monocytes (PBMo) in some patients with autism spectrum disorders (ASD). This study examined whether changes in miRNA expression by PBMo are associated with changes in IL-1ß/IL-10 ratios and how such changes are associated with ASD clinical features.MethodsmiRNA expression by purified PBMo from ASD subjects (N = 69) and non-ASD controls (N = 27) were determined by high-throughput sequencing. Cytokine production by PBMo in responses to stimuli of innate immunity, and behavioral symptoms [assessed by aberrant behavioral checklist (ABC)] were also evaluated at the same time of sample obtainment.ResultsAs a whole, there was no difference in miRNA expression between ASD and control non-ASD PBMo. However, when ASD cells were subdivided into 3 groups with high, normal, or low IL-1ß/IL-10 ratios as defined in the “Results” section, in comparison with the data obtained from non-ASD controls, we observed marked changes in miRNA expression. Namely, over 3-fold changes in expression of miR-181a, miR-93, miR-223, miR-342, and miR-1248 were observed in ASD PBMo with high or low IL-1ß/IL-10 ratios, but not in ASD PBMo with normal ratios. These miRNAs that had altered in expression are those closely associated with the regulation of key signaling pathways. With changes in IL-1ß/IL-10 ratios, we also observed changes in the production of cytokines (IL-6, TNF-α, and TGF-ß) other than IL-1ß/IL-10 by ASD PBMo. The association between behavioral symptoms and cytokine levels was different when ASD cells exhibit high/low IL-1ß/IL-10 ratios vs. when ASD cells exhibited normal ratios. Non-IgE-mediated food allergy was also observed at higher frequency in ASD subjects with high/low IL-1ß/IL-10 ratios than with normal ratios.ConclusionsChanges in cytokine profiles and miRNA expression by PBMo appear to be associated with changes in ASD behavioral symptoms. miRNAs that are altered in expression in ASD PBMo with high/low IL-1ß/IL-10 ratios are those associated with inflammatory responses. Changes in IL-1ß/IL-10 ratios along with changes in miRNA expression may serve as biomarkers for immune-mediated inflammation in ASD.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1003-6) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Fig. 1 IL-1β/IL-10 ratios under cultures without a stimulus and with stimuli (LPS, zymosan, CL097, and β-lactam).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study)

Jyonouchi

Geng

Streck

et al. 2017

J Neuroinflammation

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Variations in Mitochondrial Respiration Differ in IL-1ß/IL-10 Ratio Based Subgroups in Autism Spectrum Disorders

et al. 2019

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Autism spectrum disorder (ASD) 7 is associated with multiple physiological abnormalities, including immune dysregulation, and mitochondrial dysfunction. However, an association between these two commonly reported abnormalities in ASD has not been studied in depth. This study assessed the association between previously identified alterations in cytokine profiles by ASD peripheral blood monocytes (PBMo) and mitochondrial dysfunction. In 112 ASD and 38 non-ASD subjects, cytokine production was assessed by culturing purified PBMo overnight with stimuli of innate immunity. Parameters of mitochondrial respiration including proton-leak respiration (PLR), ATP-linked respiration (ALR), maximal respiratory capacity (MRC), and reserve capacity (RC) were measured in peripheral blood mononuclear cells (PBMCs). The ASD samples were analyzed by subgrouping them into high, normal, and low IL-1ß/IL-10 ratio groups, which was previously shown to be associated with changes in behaviors and PBMo miRNA expression. MRC, RC, and RC/PLR, a marker of electron transport chain (ETC) efficiency, were higher in ASD PBMCs than controls. The expected positive associations between PLR and ALR were found in control non-ASD PBMCs, but not in ASD PBMCs. Higher MRC, RC, RC/PLR in ASD PBMCs were secondary to higher levels of these parameters in the high and normal IL-1ß/IL-10 ratio ASD subgroups than controls. Associations between mitochondrial parameters and monocyte cytokine profiles differed markedly across the IL-1ß/IL-10 ratio based ASD subgroups, rendering such associations less evident when ASD samples as a whole were compared to non-ASD controls. Our results indicate for the first time, an association between PBMC mitochondrial function and PBMo cytokine profiles in ASD subjects. This relationship differs across the IL-1ß/IL-10 ratio based ASD subgroups. Changes in mitochondrial function are likely due to adaptive changes or mitochondrial dysfunction, resulting from chronic oxidative stress. These results may indicate alteration in molecular pathways affecting both the immune system and mitochondrial function in some ASD subjects.

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Serum microRNAs in ASD: Association With Monocyte Cytokine Profiles and Mitochondrial Respiration

et al. 2019

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Our previous research has shown that purified peripheral blood monocytes (PRMo) from individuals who are diagnosed with autism spectrum disorders (ASDs) and have innate immune abnormalities reveal altered interleukin-1ß (IL-1ß)/IL-10 ratios. We also found, in separate studies, that microRNA (miRNA) expression in PBMo and mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) differed in the IL-1ß/IL-10-based ASD subgroups. This study explored whether serum miRNAs are associated with both altered innate immune responses and changes in mitochondrial respiration as a link of regulatory mechanisms for these two common abnormalities in ASD subjects. Serum miRNA levels were examined by high-throughput deep sequencing in ASD and non-ASD control sera with concurrent measurement of PBMo cytokine production and mitochondrial respiration by PBMCs. ASD samples were examined as a whole group and with respect to the previously defined IL-1ß/IL-10-based ASD subgroups (high, normal, and low groups). Serum miRNA levels differed between the overall ASD sera (N = 116) and non-ASD control sera (N = 35) and also differed across the IL-1ß/IL-10-based ASD subgroups. Specifically, miRNA levels were increased and decreased in eight and nine miRNAs, respectively, in the high-ratio ASD subgroup (N = 48). In contrast, the low- (N = 25) and normal- (N = 43) ratio ASD subgroups only showed decreased miRNAs levels (18 and 10 miRNAs, respectively). Gene targets of the altered miRNAs in the high and/or low IL-1β/IL-10 ratio ASD subgroups were enriched in pathways critical for monocyte functions and metabolic regulation. Gene targets of the altered miRNAs in all the ASD subgroups were enriched in pathways of neuronal development and synaptic plasticity, along with cell proliferation/differentiation. ASD subgroup-specific associations were observed between serum miRNA expression and IL-1ß/IL-10 ratios, mitochondrial respiration, and monocyte cytokine profiles (IL-10, CCL2, and TNF-α). In summary, our results indicate that serum levels of select miRNAs may serve as promising biomarkers for screening and monitoring changes in innate immunity and mitochondrial respiration in ASD.

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Interleukin-1β/Interleukin10 Ratio Produced by Monocytes as a Biomarker of Neuroinflammation in Autism

Cited by 5 publications

References 35 publications

MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study)

MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study)

Variations in Mitochondrial Respiration Differ in IL-1ß/IL-10 Ratio Based Subgroups in Autism Spectrum Disorders

Serum microRNAs in ASD: Association With Monocyte Cytokine Profiles and Mitochondrial Respiration

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