Comment : Utopianism and Communitarianism

千葉大学公共研究センター21世紀プログラム「持続可能な福祉社会に向けた公共研究拠点

Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects

<div><p>Background</p><p>Type 1 diabetes mellitus is a chronic inflammatory disease involving insulin producing β-cells destroyed by the conjoined action of auto reactive T-cells, inflammatory cytokines and monocytic cells. The aim of this study was to elucidate the status of pro-inflammatory cytokines and biochemical markers and possible correlation of these factors towards outcome of the disease.</p><p>Methods</p><p>The study was carried out on 29 T1D subjects and 20 healthy subjects. Plasma levels of oxidative stress markers, enzymatic and non-enzymatic antioxidants were estimated employing biochemical assays. The levels of pro-inflammatory cytokines such as by IL-1β & IL-17 in the serum were determined by ELISA, while the expression of TNF-α, IL-23 & IFN-γ was ascertained by qRT-PCR.</p><p>Results</p><p>The onset of T1D disease was accompanied with elevation in levels of Plasma malondialdehyde, protein carbonyl content and nitric oxide while plasma vitamin C, reduced glutathione and erythrocyte sulfhydryl groups were found to be significantly decreased in T1D patients as compared to healthy control subjects. Activity of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase showed a significant suppression in the erythrocytes of T1D patients as compared to healthy subjects. Nevertheless, the levels of pro-inflammatory cytokines IL-1β and IL-17A were significantly augmented (***p≤.001) on one hand, while expression of T cell based cytokines IFN-γ, TNF-α and IL-23 was also up-regulated (*p≤.05) as compared to healthy human subjects.</p><p>Conclusion</p><p>The level of pro-inflammatory cytokines and specific biochemical markers in the serum of the patient can be exploited as potential markers for type 1 diabetes pathogenesis. The study suggests that level of inflammatory markers is up-regulated in T1D patients in an age dependent manner.</p></div

Changes in the level of pro-inflammatory cytokines in the T1D patients with varying blood glucose threshold.

<p>Serum levels of pro-inflammatory cytokines (A) IL-1β (B) IL-17A and expression level of cytokines (C) IFN-γ and (D) TNF-α in healthy control subjects and T1D patients with fasting blood sugar (BS) ≤160 mg/dl and >160 mg/dl. Data represent mean ± Standard Deviation from three separate experiments. Statistical significance was determined by unpaired student’s t-test and represented as *p≤0.05, **p<0.01 and ***p<0.001. p≤0.05 was considered statistically significant.</p

Biochemical and clinical parameters in healthy and T1D patients with fasting blood sugar (BS) ≤160 mg/dl and (BS) >160mg/dl.

<p>Biochemical and clinical parameters in healthy and T1D patients with fasting blood sugar (BS) ≤160 mg/dl and (BS) >160mg/dl.</p

Up-regulation of IL-23 expression in T1D patients.

<p>mRNA expression level of cytokine IL-23 in T1D patients, (A) with varying blood sugar level (B) with the progression of age, when compared to healthy control subjects. Data represent mean ± Standard Deviation from three separate experiments. Statistical significance was determined by unpaired student’s t-test. The p values represented as *p≤0.05, **p<0.01 and ***p<0.001 were considered statistically significant.</p

Changes in the level of pro-inflammatory cytokines in the T1D patients with age.

<p>Serum levels of pro-inflammatory cytokines (A) IL-1β (B) IL-17A and expression fold in the whole blood of pro-inflammatory cytokines (C) IFN-γ and (D) TNF-α in healthy control subjects and T1D patients of age groups ≤15 years and >15 years. Data represent mean ± Standard Deviations from three separate experiments. Statistical significance was determined by unpaired student’s t-test and represented as *p≤0.05, **p<0.01 and ***p<0.001. p≤0.05 was considered statistically significant.</p

Biochemical parameters of healthy control subjects and T1D patients with fasting blood sugar (BS) ≤160 mg/dl and >160mg/dl.

<p>Biochemical parameters of healthy control subjects and T1D patients with fasting blood sugar (BS) ≤160 mg/dl and >160mg/dl.</p

Shift in the activity of erythrocyte antioxidant enzymes with age and glycemic condition of the T1D patients.

<p>(A) Activity of erythrocyte antioxidant enzymes SOD, CAT, GR and GST in healthy control subjects and T1D patients of age groups ≤15 years and >15 years. (B) Activity of erythrocyte antioxidant enzymes SOD, CAT, GR and GST in healthy control subjects and T1D patients with fasting blood sugar (BS) ≤160 mg/dl and >160 mg/dl. Data represent mean ± S.D. Statistical significance was determined by unpaired student’s t-test and represented as *p≤0.05, **p<0.01 and ***p<0.001. p≤0.05 was considered statistically significant.</p

Variations in the level of plasma Nitric oxide with age and glycemic condition of the T1D patients.

<p>Plasma Nitric Oxide levels in healthy control subjects and T1D patients grouped on the basis of (A) age (≤15 years and >15 years) and (B) fasting blood glucose levels (≤160 mg/dl and >160 mg/dl). Data represent mean ± S.D. Statistical significance was determined by unpaired student’s t-test and represented as *p≤0.05, **p<0.01 and ***p<0.001. p≤0.05 was considered statistically significant.</p