Association of serum interleukin-6, interleukin-8, and Acute Physiology and Chronic Health Evaluation II score with clinical outcome in patients with acute respiratory distress syndrome

Deme, Swaroopa; Kakarla, Bhaskar; Mahathi, T; Katkam, Shivakrishna; Raju, Y.S.N.; Chandra, Naval; Kutala, Vijay Kumar

doi:10.4103/0972-5229.190369

Cited by 39 publications

(39 citation statements)

References 34 publications

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“…IL-6 is a potent pro-inflammatory cytokine that plays a key role in the pathogenesis of various inflammatory disorders, such as ARDS. Increased levels of both IL-8 and IL-6 have been shown to be highly correlated with the incidence of ARDS and overall mortality [ 72 – 74 ]. The concomitant increase in IFN-γ following IL-12 secretion by hMSCs under hypoxia was expected since IL-12 promotes the production of IFN-γ.…”

Section: Discussionmentioning

confidence: 99%

Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells

et al. 2018

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BackgroundIn the bone marrow, MSCs reside in a hypoxic milieu (1–5% O2) that is thought to preserve their multipotent state. Typically, in vitro expansion of MSCs is performed under normoxia (~ 21% O2), a process that has been shown to impair their function. Here, we evaluated the characteristics and function of MSCs cultured under hypoxia and hypothesized that, when compared to normoxia, dedicated hypoxia will augment the functional characteristics of MSCs.MethodsHuman and porcine bone marrow MSCs were obtained from fresh mononuclear cells. The first study evaluated MSC function following both long-term (10 days) and short-term (48 h) hypoxia (1% O2) culture. In our second study, we evaluated the functional characteristics of MSC cultured under short-term 2% and 5% hypoxia. MSCs were evaluated for their metabolic activity, proliferation, viability, clonogenicity, gene expression, and secretory capacity.ResultsIn long-term culture, common MSC surface marker expression (CD44 and CD105) dropped under hypoxia. Additionally, in long-term culture, MSCs proliferated significantly slower and provided lower yields under hypoxia. Conversely, in short-term culture, MSCs proliferated significantly faster under hypoxia. In both long-term and short-term cultures, MSC metabolic activity was significantly higher under hypoxia. Furthermore, MSCs cultured under hypoxia had upregulated expression of VEGF with concomitant downregulation of HMGB1 and the apoptotic genes BCL-2 and CASP3. Finally, in both hypoxia cultures, the pro-inflammatory cytokine, IL-8, was suppressed, while levels of the anti-inflammatories, IL-1ra and GM-CSF, were elevated in short-term hypoxia only.ConclusionsIn this study, we demonstrate that hypoxia augments the therapeutic characteristics of both porcine and human MSCs. Yet, short-term 2% hypoxia offers the greatest benefit overall, exemplified by the increase in proliferation, self-renewing capacity, and modulation of key genes and the inflammatory milieu as compared to normoxia. These data are important for generating robust MSCs with augmented function for clinical applications.

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Section: Discussionmentioning

confidence: 99%

Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells

et al. 2018

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“…Phillips et al [ 31 ] had shown that the lung injury score of non-survivors was significantly higher than that of survivors in patients with ARDS. Swaroopa et al [ 32 ] had shown that the APACHE II score was significantly higher in non-survivors as compared to survivors in patients with ARDS. In this study it was found that the APACHE II, ALIS, PaO 2 /FIO 2 and AaDO 2 were not significantly different between the survived and non-survived ARDS patients; instead, the HFP and TP were found to be the independent predictors of mortality in ARDS patients on admission to the SICU ( p < 0.05).…”

Section: Discussionmentioning

confidence: 99%

High-frequency power of heart rate variability can predict the outcome of thoracic surgical patients with acute respiratory distress syndrome on admission to the intensive care unit: a prospective, single-centric, case-controlled study

et al. 2018

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BackgroundThe morbidity and mortality of acute respiratory distress syndrome (ARDS) remains high, and the strategic focus of ARDS research has shifted toward identifying patients at high risk of mortality early in the course of illness. This study intended to identify the heart rate variability (HRV) measure that can predict the outcome of patients with ARDS on admission to the surgical intensive care unit (SICU).MethodsPatients who had lung or esophageal cancer surgery were included either in the ARDS group (n = 21) if they developed ARDS after surgery or in the control group (n = 11) if they did not. The ARDS patients were further stratified into survivors and non-survivors subgroups according to their outcomes. HRV measures of the patients were used for statistical analysis.ResultsThe mean RR interval (mRRI), high-frequency power (HFP) and product of low-/high-frequency power ratio tidal volume and tidal volume (LHR*VT) were significantly lower (p < 0.05), while the normalized HFP to VT ratio (nHFP/VT) was significantly higher in the ARDS patients (p = 0.011). The total power (TP), low-frequency power (LFP), HFP and HFP/VT were all significantly higher in the non-survived ARDS patients, whereas Richmond Agitation-Sedation Scale (RASS) was significantly lower in the non-survived ARDS patients. After adjustment for RASS, age and gender, firth logistic regression analysis identified the HFP, TP as the significant independent predictors of mortality for ARDS patients.ConclusionsThe vagal modulation of thoracic surgical patients with ARDS was enhanced as compared to that of non-ARDS patients, and the non-survived ARDS patients had higher vagal activity than those of survived ARDS patients. The vagal modulation-related parameters such as TP and HFP were independent predictors of mortality in patients with ARDS on admission to the SICU, and the HFP was found to be the best predictor of mortality for those ARDS patients. Increased vagal modulation might be an indicator for poor prognosis in critically ill patients following thoracic surgery.

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“…https://doi.org/10.1371/journal.pbio.3000970.g003 prognoses of acute respiratory distress syndrome and sepsis using IL-6 expression levels have also been established [55][56][57]. IL-6 also has a significantly increased expression level in the human bronchial epithelial cells infected with SARS-CoV-2 from the SARS2-DEG dataset [21].…”

Section: Network-based Measurement Of Covid-19-associated Disease Manmentioning

confidence: 99%

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19

et al. 2020

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The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, disease manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus–host protein–protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measurement revealed underlying pathogenesis for broad COVID-19-associated disease manifestations. Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2). To prioritize potential treatments, we combined network-based prediction and a propensity score (PS) matching observational study of 26,779 individuals from a COVID-19 registry. We identified that melatonin usage (odds ratio [OR] = 0.72, 95% CI 0.56–0.91) is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription–polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers (OR = 0.70, 95% CI 0.54–0.92) or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52–0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31–0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19.

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Association of serum interleukin-6, interleukin-8, and Acute Physiology and Chronic Health Evaluation II score with clinical outcome in patients with acute respiratory distress syndrome

Cited by 39 publications

References 34 publications

Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells

Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells

High-frequency power of heart rate variability can predict the outcome of thoracic surgical patients with acute respiratory distress syndrome on admission to the intensive care unit: a prospective, single-centric, case-controlled study

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19

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