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Type I Vs. Type II Cytokine Levels as a Function of SOD1 G93A Mouse Amyotrophic Lateral Sclerosis Disease Progression.

Jeyachandran A, Mertens B, McKissick EA, Mitchell CS - Front Cell Neurosci (2015)

Bottom Line: A significant increase in TG cytokine levels was found when compared to WT cytokine levels across the entire SOD1 G93A lifespan for majority of the cytokines.The rates of change of the individual cytokines, and type I and type II were not significantly different; however, the mean fold change of type I was expressed at significantly higher levels than type II levels across all stages with the difference between the means becoming more pronounced at the end stage.Very early immunoregulatory treatment is necessary to successfully interrupt ALS-induced neuroinflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University Atlanta, GA, USA.

ABSTRACT
Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease that is characterized by the degradation of neurons throughout the central nervous system. Inflammation have been cited a key contributor to ALS neurodegeneration, but the timeline of cytokine upregulation remains unresolved. The goal of this study was to temporally examine the correlation between the varying levels of pro-inflammatory type I cytokines (IL-1β, IL-1α, IL-12, TNF-α, and GFAP) and anti-inflammatory type II cytokines (IL-4, IL-6, IL-10) throughout the progression of ALS in the SOD1 G93A mouse model. Cytokine level data from high copy SOD1 G93A transgenic mice was collected from 66 peer-reviewed studies. For each corresponding experimental time point, the ratio of transgenic to wild type (TG/WT) cytokine was calculated. One-way ANOVA and t-tests with Bonferonni correction were used to analyze the data. Meta-analysis was performed for four discrete stages: early, pre-onset, post-onset, and end stage. A significant increase in TG cytokine levels was found when compared to WT cytokine levels across the entire SOD1 G93A lifespan for majority of the cytokines. The rates of change of the individual cytokines, and type I and type II were not significantly different; however, the mean fold change of type I was expressed at significantly higher levels than type II levels across all stages with the difference between the means becoming more pronounced at the end stage. An overexpression of cytokines occurred both before and after the onset of ALS symptoms. The trend between pro-inflammatory type I and type II cytokine mean levels indicate a progressive instability of the dynamic balance between pro- and anti-inflammatory cytokines as anti-inflammatory cytokines fail to mediate the pronounced increase in pro-inflammatory cytokines. Very early immunoregulatory treatment is necessary to successfully interrupt ALS-induced neuroinflammation.

No MeSH data available.


Related in: MedlinePlus

Normalized cytokine levels over time separated by the four stages utilized for statistical analysis, early (0–76 days), pre-onset (77–96 days), post-onset (97–116 days), and end stages (117–135 stages). (A). Plot of all raw data cytokine ratios (TG/WT) for type I and type II cytokines. (B). Cytokines ratios (TG/WT) for type I cytokines only. (C). Cytokine ratios (TG/WT) for type II cytokines only.
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Figure 2: Normalized cytokine levels over time separated by the four stages utilized for statistical analysis, early (0–76 days), pre-onset (77–96 days), post-onset (97–116 days), and end stages (117–135 stages). (A). Plot of all raw data cytokine ratios (TG/WT) for type I and type II cytokines. (B). Cytokines ratios (TG/WT) for type I cytokines only. (C). Cytokine ratios (TG/WT) for type II cytokines only.

Mentions: Experimental in vivo data on cytokines levels in transgenic (TG) SOD1 G93A ALS mice and wild type (WT) mice was utilized from a total of 66 peer-reviewed articles, which met the study inclusion criteria. The ratio of TG to WT cytokine levels at each examined time point was calculated, resulting in total of 266 TG/WT ratios. TG/WT cytokine level ratio is plotted for each specific cytokine type over the TG mouse life span (Figure 1). Figure 2A illustrates the data included in our meta-analysis, separated by disease stage. Individual cytokines are aggregated and presented by their corresponding type, type I (Figure 2B) or II (Figure 2C). Since pro-inflammatory type I cytokines are generally viewed as having a larger role in the progression of ALS, type II (IL-4, IL-6, and IL-12) cytokines have been less studied in the experimental literature; consequently, there is less type II cytokine data.


Type I Vs. Type II Cytokine Levels as a Function of SOD1 G93A Mouse Amyotrophic Lateral Sclerosis Disease Progression.

Jeyachandran A, Mertens B, McKissick EA, Mitchell CS - Front Cell Neurosci (2015)

Normalized cytokine levels over time separated by the four stages utilized for statistical analysis, early (0–76 days), pre-onset (77–96 days), post-onset (97–116 days), and end stages (117–135 stages). (A). Plot of all raw data cytokine ratios (TG/WT) for type I and type II cytokines. (B). Cytokines ratios (TG/WT) for type I cytokines only. (C). Cytokine ratios (TG/WT) for type II cytokines only.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664727&req=5

Figure 2: Normalized cytokine levels over time separated by the four stages utilized for statistical analysis, early (0–76 days), pre-onset (77–96 days), post-onset (97–116 days), and end stages (117–135 stages). (A). Plot of all raw data cytokine ratios (TG/WT) for type I and type II cytokines. (B). Cytokines ratios (TG/WT) for type I cytokines only. (C). Cytokine ratios (TG/WT) for type II cytokines only.
Mentions: Experimental in vivo data on cytokines levels in transgenic (TG) SOD1 G93A ALS mice and wild type (WT) mice was utilized from a total of 66 peer-reviewed articles, which met the study inclusion criteria. The ratio of TG to WT cytokine levels at each examined time point was calculated, resulting in total of 266 TG/WT ratios. TG/WT cytokine level ratio is plotted for each specific cytokine type over the TG mouse life span (Figure 1). Figure 2A illustrates the data included in our meta-analysis, separated by disease stage. Individual cytokines are aggregated and presented by their corresponding type, type I (Figure 2B) or II (Figure 2C). Since pro-inflammatory type I cytokines are generally viewed as having a larger role in the progression of ALS, type II (IL-4, IL-6, and IL-12) cytokines have been less studied in the experimental literature; consequently, there is less type II cytokine data.

Bottom Line: A significant increase in TG cytokine levels was found when compared to WT cytokine levels across the entire SOD1 G93A lifespan for majority of the cytokines.The rates of change of the individual cytokines, and type I and type II were not significantly different; however, the mean fold change of type I was expressed at significantly higher levels than type II levels across all stages with the difference between the means becoming more pronounced at the end stage.Very early immunoregulatory treatment is necessary to successfully interrupt ALS-induced neuroinflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Georgia Institute of Technology and Emory University Atlanta, GA, USA.

ABSTRACT
Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease that is characterized by the degradation of neurons throughout the central nervous system. Inflammation have been cited a key contributor to ALS neurodegeneration, but the timeline of cytokine upregulation remains unresolved. The goal of this study was to temporally examine the correlation between the varying levels of pro-inflammatory type I cytokines (IL-1β, IL-1α, IL-12, TNF-α, and GFAP) and anti-inflammatory type II cytokines (IL-4, IL-6, IL-10) throughout the progression of ALS in the SOD1 G93A mouse model. Cytokine level data from high copy SOD1 G93A transgenic mice was collected from 66 peer-reviewed studies. For each corresponding experimental time point, the ratio of transgenic to wild type (TG/WT) cytokine was calculated. One-way ANOVA and t-tests with Bonferonni correction were used to analyze the data. Meta-analysis was performed for four discrete stages: early, pre-onset, post-onset, and end stage. A significant increase in TG cytokine levels was found when compared to WT cytokine levels across the entire SOD1 G93A lifespan for majority of the cytokines. The rates of change of the individual cytokines, and type I and type II were not significantly different; however, the mean fold change of type I was expressed at significantly higher levels than type II levels across all stages with the difference between the means becoming more pronounced at the end stage. An overexpression of cytokines occurred both before and after the onset of ALS symptoms. The trend between pro-inflammatory type I and type II cytokine mean levels indicate a progressive instability of the dynamic balance between pro- and anti-inflammatory cytokines as anti-inflammatory cytokines fail to mediate the pronounced increase in pro-inflammatory cytokines. Very early immunoregulatory treatment is necessary to successfully interrupt ALS-induced neuroinflammation.

No MeSH data available.


Related in: MedlinePlus