&lt;p&gt;Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus&lt;/p&gt;

Kartika, Rona; Purnamasari, Dyah; Pradipta, Saraswati; Larasati, Rahma Ayu

doi:10.2147/jir.s245064

Cited by 32 publications

(20 citation statements)

References 29 publications

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“…39 Surprisingly, IFN-γ revealed a significant negative correlation with HbA1c and LDL. This was in contrast to Kartika et al 30 , who demonstrated that IFN-γ is known to stimulate proinflammatory macrophage of M1 phenotype which potentiates the development of T2DM.…”

Section: Discussioncontrasting

confidence: 81%

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T-Natural Killers and Interferon Gamma/Interleukin 4 in Augmentation of Infection in Foot Ulcer in Type 2 Diabetes

Hammad

Elmadbouly

Ahmad

et al. 2021

DMSO

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Background The link between immune system and type 2 diabetes mellitus (T2DM) pathogenesis attracted attention to demonstrate the role of immune cells and their secreted cytokines in T2DM development and its subsequent foot complications. Objective To investigate the relation between T Natural killer cell (TNK) %, Interleukin 4 (IL4) and Interferon gamma (IFN-γ) and diabetic foot infection (DFI) development in patients with diabetic foot ulcer (DFU). Patients and Methods Ninety patients with diabetes were included in this work, divided as T2DM group (n=30), DFU group (n=30), and DFI group (n=30). TNK% was detected using flow cytometry. Serum IL4 and IFN-γ were measured by ELISA. Diabetes biochemical parameters were also analyzed. Results Significant decrease was detected in TNK% and IFN-γ in DFI group compared to other 2 groups ( P <0.001). Significant decrease was detected in serum levels of IL4 in DFI group compared to T2DM group ( P =0.006). IFN-γ/IL4 was significantly decreased in DFI compared to DFU group ( P =0.020). There was a significant correlation of TNK% with both IL4 and IFN-γ (r=0.385, P <0.001; r=0.534, P <0.001, respectively). Significant negative correlation of TNK% with HbA1c and LDL was revealed (r=−0.631, P <0.001; and r=−0.261, P =0.013, respectively), while a positive correlation was seen with HDL (r=0.287, P =0.006). A significant negative correlation of IL4 with HbA1c was found (r=−0.514, P <0.001;. As for IFN-γ, a significant negative correlation with HbA1c and LDL was detected (r=−0.369, P < 0.001; r=−0.229, P =0.030). TNK % and IFN-γ level showed negative correlations with disease duration/year (r=−0.546, P < 0.001; r=−0.338, P =0.001,respectively). Conclusion Decline in TNK frequency has essential role in T2DM pathogenesis and subsequent foot complications. Downregulation of TNK% and IFN-γ level have potential roles in predicting infection of diabetic ulcer and are correlated with disease duration.

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Section: Discussioncontrasting

confidence: 81%

“…Tsiavou et al 29,30 and Kartika et al documented the reduction in IFN-γ production in T2DM. Also, Schmohl et al 31 reported that IFN-γ was not detected in wound fluid extracted from DFU with or without infection, whereas 100% recovery was found for IFN-γ during wound recovery.…”

Section: Discussionmentioning

confidence: 99%

T-Natural Killers and Interferon Gamma/Interleukin 4 in Augmentation of Infection in Foot Ulcer in Type 2 Diabetes

Hammad

Elmadbouly

Ahmad

et al. 2021

DMSO

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“…Moreover, T-cells function is significantly dysregulated in T2D and CD4 + lymphocytes preferentially differentiate in T-helper 1 and T-helper 17 instead of T-helper 2 with a consequent imbalance between pro-inflammatory and anti-inflammatory activities [ 70 ]. On the other hand, the levels of interferon gamma—which normally stimulates CD4 + T cells maturation in sense of T-helper 1 rather than T-helper 2—were found to be lower in T2D patients sera, and can contribute in a blunted T-cell response in T2D [ 71 ]. Nevertheless, lower levels of interleukin (IL)-10 have also been described in T2D patients.…”

Section: Immune System Responsementioning

confidence: 99%

“…Nevertheless, lower levels of interleukin (IL)-10 have also been described in T2D patients. Considering that IL-10 is capable to suppress the release of pro-inflammatory cytokines, lower levels of IL-10 could be related with higher IL-6-to-IFN gamma and TNF-alpha-to-IFN gamma ratios hence suggesting an enhanced activation of circulating monocytes [ 71 ]. High levels of IL-6 have been detected in diabetic patients respective to those with euglycemia, suggesting that hyperglycaemia play a crucial role in determining this immunological effect [ 72 , 73 ].…”

Section: Immune System Responsementioning

confidence: 99%

Hypothesized mechanisms explaining poor prognosis in type 2 diabetes patients with COVID-19: a review

et al. 2020

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Purpose Epidemiological data suggest that comorbid patients, mostly those with type 2 diabetes (T2D), are predisposed to poor prognosis in Coronavirus disease 2019 (COVID-19), leading to serious healthcare concerns. The aim of the present manuscript is to review the main relevant mechanisms possibly contributing to worsen the clinical course of COVID-19 in T2D. Results Poor glucose control, high glycaemic variability and diabetes-related comorbidities at baseline, particularly cardiovascular diseases and obesity, contribute in worsening the prognosis in the above-mentioned cluster of patients. Moreover, both a lower efficient innate immune system response and cytokine dysregulation predispose patients with T2D to impaired viral clearance and more serious pulmonary and systemic inflammation once the SARS-CoV-2 infection occurred. Inconclusive data are currently available for specifically indicate or contraindicate concurrent medications for managing T2D and its comorbidities in infected patients. Conclusions T2D individuals should be considered as more vulnerable to COVID-19 than general population, and thus require adequate advices about hygienic tips to protect themselves during the pandemic. A careful management of glucose levels and diabetes-related comorbidities remains essential for avoiding further complications, and patient monitoring during the pandemic should be performed also at distance by means of telemedicine. Further studies are needed to clarify whether medications normally used for managing T2D and its associated comorbidities could have a protective or detrimental effect on COVID-19 clinical course.

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“…3,12 In the serum of the patients with systematic inflammation, levels of pro-inflammatory and pro-fibrotic cytokines, metabolites and other pathological factors are usually elevated. 13,14 These factors promote macrophagespolarization and fibroblastsactivation via NF-κB, Smads and other pathways, [15][16][17] and are potential biomarkers and drivers of liver, 18 renal 19 or lung fibrosis. 20 Similarly, for FS, it is also characterized by capsular fibrosis, during which macrophages and fibroblasts are the two pivotal cellular players.…”

Section: Introductionmentioning

confidence: 99%

The Serum from Patients with Secondary Frozen Shoulder Following Rotator Cuff Repair Induces Shoulder Capsule Fibrosis and Promotes Macrophage Polarization and Fibroblast Activation

Sun

Lin

Luo

et al. 2021

JIR

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Disorders with systematic inflammation were prognostic for secondary frozen shoulder (sFS) following rotator cuff repair (RCR); however, how systematic inflammation affects sFS remains unclear. The aim of this study was to observe the effect of pre-operative serum from patients with sFS and the serum from those without on shoulder capsule in mice, and on macrophages and fibroblasts in vitro. Methods: Serum samples of a consecutive cohort of patients for RCR were collected preoperatively. Three months after RCR, patients who developed sFS (Group S) were identified. Serum samples from gender-and age-matched controls without sFS (group NS) were also picked out. Firstly, the effect of serum on shoulder capsule fibrosis was observed histologically and biomechanically in a mouse model of RCR. Secondly, the roles of the serum on macrophage polarization and fibroblast activation were investigated, and the potentially involved signaling pathways were identified. Finally, inflammation and fibrosis-related cytokines in serum were quantified. Results: In our cohort, all patients had free pre-operative shoulder range of motion. Seven patients developed sFS at 3 months after surgery. Seven matched patients without sFS were selected as control. The inter-group difference of basic characteristics was not significant. Compared to the serum of group NS, the serum of group S significantly induced hypercellularity, capsular thickening, and range of motion deficiency in mice shoulders after RCR. Compared to the serum of group NS, samples of group S significantly promoted M2 polarization of THP-1 human macrophages and the activation of human capsule-derived fibroblasts. Meanwhile, Smad3 and p-Smad3 in macrophages and fibroblasts were significantly up-regulated. On the other hand, levels of inflammation and fibrosis-related cytokines were not significantly different between serum in group S and group NS. Conclusion: Although all patients in this cohort had free range of motion pre-operatively, the pre-operative serum from patients with sFS at 3 months after RCR could act as a trigger of shoulder capsule fibrosis post-operatively. This effect may be related to its promotion on macrophage polarization to M2 phenotype and fibroblast activation.

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<p>Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus</p>

Cited by 32 publications

References 29 publications

T-Natural Killers and Interferon Gamma/Interleukin 4 in Augmentation of Infection in Foot Ulcer in Type 2 Diabetes

T-Natural Killers and Interferon Gamma/Interleukin 4 in Augmentation of Infection in Foot Ulcer in Type 2 Diabetes

Hypothesized mechanisms explaining poor prognosis in type 2 diabetes patients with COVID-19: a review

The Serum from Patients with Secondary Frozen Shoulder Following Rotator Cuff Repair Induces Shoulder Capsule Fibrosis and Promotes Macrophage Polarization and Fibroblast Activation

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