Blood Interleukin-6 Research Articles

Cooling During Endurance Cycling in the Heat: Blunted Core Temperature but Not Inflammatory Responses.

This study assessed the effects of cooling during endurance cycling (percooling) on changes in core body temperature (Tcore), inflammatory, and metabolic responses. A total of 12 male cyclists (peak oxygen uptake 60 [4]mL·kg-1·min-1) completed a 60-minute constant workload trial (55% of peak power output and ambient temperature 30.4°C [0.6°C]) in a randomized order both with (ICE) and without (CON) an ice vest. An ingestible capsule was used to measure Tcore. Blood samples were collected immediately before and after each trial to determine concentrations of blood lactate, serum cortisol, interleukin-6, and reactive oxygen and nitrogen species. Tcore increased statistically (P < .001) both in CON (7.0% [1.4%], effect size [ES] = 6.3) and ICE (5.1% [1.1%], ES = 5.7). The increase in CON was statistically larger compared with ICE (P = .006, ES = 1.4). Concentrations of blood lactate (CON: 163% [63%], ES = 1.3; ICE: 149% [91%], ES = 1.3), cortisol (CON: 138% [123%], ES = 1.7; ICE: 81% [102%], ES = 1.0), and interleukin-6 (CON: 661% [324%], ES = 2.1; ICE: 624% [368%], ES = 1.2) statistically increased in both conditions (P < .01) to a similar extent. In addition, reactive oxygen and nitrogen species statistically decreased in both conditions (CON: -19.2% [14.9%], P = .002, ES = 0.9; ICE: -15.1% [16.5%], P = .02, ES = 0.9). No correlations were found between the changes of Tcore and blood parameters across the conditions. Despite attenuated Tcore, similar inflammatory and metabolic responses were observed. Our findings suggest percooling to be a promising strategy to attenuate thermal strain without compromising physiological function.

The expression and significance of leukemia inhibitory factor, interleukin-6 and vascular endothelial growth factor in Chinese patients with endometriosis.

To observe the levels of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, and ectopic endometrial stromal cells of patients with endometriosis, and to compare expression of IL-6, LIF and VEGF expression between endometriotic and non-endometriotic patients underwent laparoscopic surgery. Thirty-one patients who underwent laparoscopic surgery for endometriosis in our hospital from January 2018 to January 2020 were included in the observation group, and 32 patients who underwent laparoscopic surgery for uterine fibroids, ovarian serous cystadenoma, and ovarian teratomas, were included in the control group. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the two groups of patients were detected. The levels of LIF, IL-6 and VEGF in ectopic endometrial tissue and self-paired eutopic endometrial tissue, ectopic endometrial stromal cells and self-paired eutopic endometrial stromal cells of patients in the observation group were detected. After treating the primary cultured ectopic endometrial stromal cells with LIF and IL-6 alone or in combination, the changes of VEGF mRNA of ectopic endometrial stromal cells and the VEGF levels in the supernatant were observed. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the observation group were all higher than those of the control group (P < 0.05), and the levels of LIF, IL-6 and VEGF in the peritoneal fluid of the observation group were significantly higher than those in the blood (P < 0.05). In the observation group, the expression levels of LIF-mRNA and IL-6 mRNA in the ectopic endometrial tissue were higher than those in the self-paired eutopic endometrial tissues (P < 0.05), while the expression level of VEGF mRNA in the ectopic endometrial tissues was lower than that in the self-paired eutopic endometrial tissues (P < 0.05). Besides, the mRNA expression levels of LIF, IL-6 and VEGF in ectopic endometrial stromal cells of the observation group were all higher than those in the self-paired eutopic endometrial stromal cells (P < 0.05). After stimulating ectopic endometrial stromal cells with LIF, IL-6 and LIF + IL-6, respectively, the VEGF levels in the supernatant were all significantly higher than that in the blank control group (P < 0.05). The LIF, IL-6 and VEGF levels in blood and peritoneal fluid were increased in patients with endometriosis, and increased LIF and IL-6 in ectopic endometriosis stromal cells can play a synergistic role in increasing the VEGF levels, which may be involved in the occurrence and development of endometriosis.

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

IL-6 Predicts Poor Early Post-Natal Growth in Very Low-Birth-Weight Infants in a Low-Middle Income Setting.

Extra-uterine growth restriction (EUGR) is common in preterms and may be associated with elevated pro-inflammatory cytokines. Describe postnatal growth in a cohort of very low-birth-weight (VLBW) infants and determine the association of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) in umbilical cord blood with growth at 40 weeks and 12 months postmenstrual age (PMA). Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019 with follow-up to 31 March 2020. Infants <1500 g at birth were enrolled, cord blood collected for IL-6 and TNF-α assays and postnatal care, including anthropometry, provided to 12 months PMA. Informed consent and ethics approval were obtained. In total, 279 patients were enrolled; 84 (30.1%) died before 12 months and 91 (32.6%) lost to follow-up. Anthropometry was available for 151 infants at 40 weeks and 105 at 12 months. Z-Scores at 40 weeks for males and females combined were -2.5, -2.1 and -1.2 for weight, length and head circumference. EUGR occurred in 103/113 (91.2%), 98/107 (91.6%) and 70/109 (64.2%) participants for weight, length and head circumference. Elevated IL-6 was associated with restricted weight (56.0 vs. 14.5 pg/ml, p = 0.02) and length (60.4 vs. 7.3 pg/ml, p = 0.01) at 40 weeks. There was no difference in IL-6 at 12 months and no difference in TNF-α at 40 weeks or 12 months. The study reports significant EUGR. Elevated IL-6 was associated with growth restriction at 40 weeks but not 12 months PMA.

Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma

AbstractAxicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated whether immune dysregulation, present before CAR T-cell therapy, was associated with treatment failure. Tumor expression of interferon (IFN) signaling, high blood levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and high blood interleukin-6 and ferritin levels were each associated with a lack of durable response. Similar to other cancers, we found that in LBCL tumors, IFN signaling is associated with the expression of multiple checkpoint ligands, including programmed cell death–ligand 1, and these were higher in patients who lacked durable responses to CAR-T therapy. Moreover, tumor IFN signaling and blood M-MDSCs associated with decreased axi-cel expansion. Finally, patients with high tumor burden had higher immune dysregulation with increased serum inflammatory markers and tumor IFN signaling. These data support that immune dysregulation in LBCL promotes axi-cel resistance via multiple mechanistic programs: insufficient axi-cel expansion associated with both circulating M-MDSC and tumor IFN signaling, which also gives rise to expression of immune checkpoint ligands.

Increased Levels of Umbilical Cord Blood Interleukin-6 (IL-6) and Serum C-Reactive Protein (CRP) in Premature Infants of Vitamin D Deficient Mothers

Objective: Increased levels of inflammatory factors in newborns are often associated with lower maternal vitamin D levels. This study aimed to find out the relationship between maternal and umbilical cord vitamin D serum levels on umbilical cord Interleukin-6 (IL-6) and serum C-Reactive Protein (CRP) levels in premature infants.Methods: The study was an observational analytic, cross-sectional design in mothers who underwent preterm birth at 28-34 weeks' gestation due to premature rupture of membranes (PROM) and their infants at Dr. Cipto Mangunkusumo General Hospital (RSCM), Jakarta and Persahabatan General Hospital, Jakarta, from January 2017 to August 2018. Levels of serum vitamin D of the maternal and umbilical cord, umbilical cord IL-6 and serum CRP in premature infants were recorded. Vitamin D level was divided into deficiency (&lt;10 ng/mL), insufficiency (10–29 ng/mL), and normal (&gt;30 ng/mL) groups. The relationship of vitamin D levels with IL-6 and CRP was carried out using Kruskal Wallis test.Results: A total of 70 subjects met the research criteria. Umbilical cord IL-6 and serum CRP levels in premature infants of vitamin D deficient mothers were higher (20.31 pg/mL and 0.50 mg/L) compared to insufficient (3.34 pg/mL and 0.45 mg/L) and normal mothers (3.29 pg/mL and 0.30 mg/L), although not statistically significant (IL-6 p = 0.665, CRP p = 0.89). Referring to the umbilical cord blood vitamin D levels, the results were different and not as expected, in which the umbilical cord IL-6 and serum CRP levels of preterm infants in the deficiency (3.76 pg/mL and 0.35 mg/L) and insufficiency (3.37 pg/mL and 0.40 mg/L) groups were lower (IL-6) and not different (CRP) than the normal group (9.41 pg/mL and 0.40 mg/L).Conclusion: There were an increasing tendency for umbilical cord IL-6 and serum CRP levels in premature infants of vitamin D deficient mothers although these were not statistically significant. Based on the levels of vitamin D umbilical cord blood, the CRP levels in the serum of premature infants were not different, while the IL-6 levels in the deficiency and insufficiency group were lower than in the normal group.Keywords: CRP, IL-6, maternal vitamin D, umbilical cord vitamin D.&#x0D; &#x0D; Abstrak&#x0D; Tujuan: Peningkatan kadar faktor inflamasi pada bayi baru lahir sering dikaitkan dengan rendahnya kadar vitamin D ibu. Penelitian ini bertujuan untuk mengetahui hubungan kadar serum vitamin D ibu dan tali pusat, dengan kadar IL-6 tali pusat dan serum C-Reactive Protein (CRP) bayi prematur.Metode: Studi observasional analitik dengan desain potong lintang pada subjek ibu yang mengalami kelahiran prematur di usia 28–34 minggu kehamilan disebabkan ketuban pecah dan bayi yang dilahirkannya, di Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo (RSCM) dan Rumah Sakit Umum Pusat Persahabatan, Jakarta, pada bulan Januari 2017 sampai Agustus 2018. Variabel data adalah kadar serum vitamin D ibu dan tali pusat, kadar serum IL-6 tali pusat dan kadar CRP darah bayi. Kadar vitamin D (25(OH)D) dibagi menjadi defisiensi (&lt;10 ng/mL), insufisiensi (10–29 ng/mL) dan normal (&gt;30 ng/mL) dan dicari hubungannya dengan kadar IL-6 tali pusat dan serum CRP bayi prematur, menggunakan uji Kruskal Wallis. Hasil: Sebanyak 70 subjek telah memenuhi kriteria penelitian. Kadar IL-6 tali pusat dan serum CRP bayi prematur dari kelompok ibu defisiensi vitamin D (20,31 pg/ml dan 0,50 mg/L) lebih tinggi dibandingkan kelompok ibu insufisiensi vitamin D (3,34 pg/mL dan 0,45 mg/L) maupun kelompok ibu normal vitamin D (3,29 pg/mL dan 0,30 mg/L) tetapi perbedaan tersebut tidak bermakna (IL-6 p=0,665 dan CRP p = 0,899). Mengacu pada kadar vitamin D darah tali pusat didapatkan hasil yang berbeda dan tidak sesuai harapan, dimana tali pusat IL-6 dan serum CRP bayi prematur mengalami defisiensi (3,76 pg / mL dan 0,35 mg / L) dan insufisiensi. (3,37 pg / mL dan 0,40 mg / L) kelompok lebih rendah (IL-6) dan tidak berbeda (CRP) dibandingkan kelompok normal (9,41 pg / mL dan 0,40 mg / L).Kesimpulan: Didapat kecenderungan peningkatan kadar IL-6 darah tali pusat dan serum CRP bayi prematur dari ibu dengan defisiensi kadar vitamin D walaupun secara statistik tidak signifikan. Berdasarkan kelompok vitamin D darah tali pusat, kadar CRP serum bayi prematur tidak berbeda, sedangkan kadar IL-6 pada kelompok defisiensi dan insufisiensi lebih rendah dibandingkan pada kelompok normal.Kata kunci: CRP, IL-6, vitamin D ibu, vitamin D tali pusat. &#x0D;

Prognostic Value of a Clinical Biochemistry-Based Nomogram for Coronavirus Disease 2019.

Background: This study aimed to explore the predictive value of a clinical biochemistry-based nomogram in COVID-19.Methods: The plasma or serum concentrations/levels of carcinoembryonic antigen (CEA) and other biomarkers, e.g., C-reactive protein (CRP), white blood cell (WBC), interleukin-6 (IL-6), ferritin (Fer), procalcitonin (PCT), lymphocyte percentage (L%), D-dimer (D2), and neutrophils percentage (Neu%), were assessed in 314 hospitalized patients with confirmed COVID-19. The area under the curve was used to estimate the diagnostic and prognostic value for COVID-19. Cox and logistic regression analyses were used to estimate the independent prognostic risk factors for the survival of patients with COVID-19.Results: Receiver operating characteristic (ROC) curves were used to determine the area under the curve (AUC) values for CEA, IL-6, CRP, PCT, Fer, D-dimer levels and L%, Neu%, and WBC to assess disease classification. The critical values for these markers to predict severe disease type were then determined. The hazard ratio of prognosis for risk of COVID-19 identified CEA, WBC, CRP, PCT, Fer, D-dimer, Neu%, and L% as independent prognostic factors. For the nomogram of overall survival (OS), the C-index was 0.84, demonstrating a good discriminative performance.Conclusions: An OS nomogram for the clinical diagnosis and treatment of COVID-19 was constructed using biomarkers. These data will be useful for the diagnosis, management, and therapy of COVID-19.

Different responses of apoptotic, inflammatory and heat shock protein gene expression to a single bout of high-intensity interval exercise between physically active and inactive men

High mechanical load of muscles may induce muscular apoptosis on the one hand and adaptation to exercise on the other. This study aimed to explore whether changes of circulatory levels of inflammation, apoptosis and heat shock proteins (HSPs) messenger RNA (mRNA) following single bout of high-intensity interval exercise (HIIE) differs between physically active (PA) and inactive (PI) men. Nine PA and 9 PI (peak oxygen consumption: 2.6 ± 0.4 vs. 2.0 ± 0.2 L·min-1) healthy men (age: 28.7 ± 6.3 vs. 30.2 ± 4.5 years and body mass index: 2.6 ± 2.1 vs. 23.3 ± 2.8 kg·m-2) performed HIIE, comprising 4 repeats of a Wingate test (load: 0.050 kg·kg-1 body weight). Blood samples were collected before exercise, 5 min after HIIE, and 24 h after HIIE for measuring mRNA of inflammation markers interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), apoptosis markers including Bcl-2, Bax, and HSP27, HSP60, HSP70, HSP90 using quantitative real-time PCR analysis. Post-HIIE IL-6, TNFα and HSP60 were higher in the PI than the PA group 5 min after exercise (p = 0.003, effect size (ES) = 1.59; p = 0.007, ES = 1.59 and p = 0.027, ES = 1.10 respectively). HSP70 acutely increased only in the PA group (p = 0.024, ES = 1.20). The increase in Bcl-2 (p = 0.047, ES = 1.08) and Bax (p = 0.024, ES = 1.20) levels were higher in the PI group 5 min after HIIE. The present study indicated that the response of inflammatory, apoptosis and HSP gene expressions to HIIE in blood of healthy male volunteers strongly depends on their level of regular physical activity. Novelty: Blood IL-6 and HSP60 mRNA levels following high intensity exercise may indicate metabolic stress. Increased blood HSP70 mRNA in physically active men may show an alternative apoptosis suppression pathway.

Blood and synovial fluid calprotectin as biomarkers to diagnose chronic hip and knee periprosthetic joint infections.

Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46-55.

Predictive model using hemoglobin, albumin, fibrinogen, and neutrophil-to-lymphocyte ratio to distinguish patients with colorectal cancer from those with benign adenoma.

Colorectal cancer (CRC) is associated with inflammation, activation of coagulation, and mild anemia. Hematological parameters reflecting ongoing cancer may have the potency to be effective for early diagnostics of CRC. The aim of this study was to examine the validity and relationship between some biochemical and hematological parameters for the early diagnosis of CRC. We designed a prospective observational cohort study to analyze whether these laboratory markers have the potency to distinguish benign tumors from malignant before planned surgery. The clinical data were collected from 208 patients with suspected benign or malignant colorectal tumors who were eligible for elective surgery between September 2018 and January 2020. Blood samples were collected one day before surgery, examined parameters included: complete blood count, hemoglobin (HGB) concentration, albumin (ALB), C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen (FG). Absolute neutrophil and lymphocyte counts were used for the calculation of the neutrophil-to-lymphocyte ratio (NLR). The diagnosis was confirmed by histopathological examination. The 197 patients were divided into the group of benign (B group = 52 patients) or malignant tumors (CRC group = 145 patients). ROC curves and cut-off values of NLR, HGB, FG, and ALB concentration, serum CRP and IL-6 levels. In the cohort of 197 adult patients submitted for the elective colorectal surgery, the complete blood samples drawn one day before surgery showed significant differences between patients with benign tumors and colorectal carcinoma: HGB (mean 139.9 g/l vs. 129.9; p<0.001), FG (mean 3.36 g/l vs. 3.94 g/l; p<0.001), ALB (mean 43.4 g/l vs. 41.1 g/l; p=0.001), NLR (mean 2.73 vs. 3.88; p=0.016), respectively. CRP (mean 2.9 mg/l vs. 4.4 mg/l; p=0.011), thrombocyte count (mean 235×109/l vs. 265×109/l; p<0.029). Differences in IL-6 concentrations were not significant (2.9 pg/ml vs. 4.15 pg/ml; p=0.052). Using multivariable logistic regression analysis, four valid parameters (HGB, FG, ALB, and NLR) were suitable for the construction of a diagnostic predictive model for the identification of CRC. In conclusion, a panel of routinely examined blood parameters like HGB, FG, ALB, and NLR has the potency to distinguish patients with benign tumors from malignant by applying a diagnostic predictive model for early laboratory detection of CRC.

Relationship between peroxisome proliferator-activated receptor-γ mRNA expression and intracranial aneurysm rupture

It has been reported that the normal adults can suffer from an intracranial aneurysm (IA) that might present the risk of rupture and cause the subarachnoid hemorrhage. Peroxisome proliferator-activated receptor-γ (PPAR-γ) as a nuclear hormone receptor has been identified to involve in the progress of the formation and rupture of IAs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect PPAR-γmRNA expression in the macrophages of the patients with IAs. The information including fasting blood glucose (FBG), interleukin-6 (IL-6), and systolic blood pressure (SBP) were collected. The aneurysm parameters of all the participants were obtained through the cerebral angiography. Establishing the receiver-operating characteristic curve (ROC curve) evaluated the clinical significances of PPAR-γmRNA for IAs rupture. In this study, we observed that the rupture of IAs was caused by the maximum height of aneurysm ⩾7 mm, the location of aneurysm in posterior communicating artery (PCOM) or anterior communicating artery (ACOM), and the increase of aneurysm size ratio (SR). The levels of SBP and IL-6 in the rupture group were higher than those in the unrupture group, and PPAR-γmRNA expression in the rupture group was also significantly reduced. In addition, heavy drinking was statistically significant between the ruptured and unruptured groups. There was no significant difference in serum FBG level between the two groups. The evidences of this study showed that PPAR-γmRNA was negatively correlated with SBP, SR, and IL-6 levels in rupture group, respectively. The AUC of PPAR-γmRNA in ROC curve was 0.867, indicating that the change of PPAR-γmRNA level had obvious effect on IAs rupture. The aim of this study was to evaluate the potential of PPAR-γ in macrophages to prevent IAs rupture.

Hyponatremia in Coronavirus Disease-19 Patients: A Retrospective Analysis.

Background:Hyponatremia (serum Na+ < 135 mmol/L) is the most common electrolyte abnormality detected in clinical practice and an important cause of mortality and morbidity in hospital settings. Hyponatremia in patients with pneumonia is usually mild but is associated with increased risk of intensive care unit (ICU) admission, prolonged hospital stays, and increased mortality rates. The purpose of this study is to understand the impact of varying degrees of hyponatremia and various other inflammatory markers on the severity and outcome of coronavirus disease-19 (COVID-19).Objective:The main objective of this study is to evaluate the prevalence of hyponatremia in COVID-19 patients and to assess the correlation between hyponatremia and severity and outcome of COVID-19. The other objective is to evaluate the correlation between various inflammatory markers and outcome (ICU vs non-ICU admission, discharged vs deceased) in patients with COVID-19 pneumonia.Methods:A total of 113 participants who have been diagnosed with COVID-19 infection by reverse transcriptase-polymerase chain reaction test were included in the study. Epidemiological, demographic, clinical, investigative work-up, and outcome data were extracted from electronic health records using a standard data collection form. Based on serum sodium levels, patients were divided into two groups: normonatremic (serum Na+ ≥ 135 mEq/L) and hyponatremic (serum Na+ < 135 mEq/L). Various clinical, laboratory, and outcome parameters were compared between the two groups.Results:Hyponatremia was present in 50 out of 113 (44%) patients in our study, and it was generally mild. There were more male patients in hyponatremia group (P = .006), and hyponatremic patients were older than normonatremic patients (P = .001). Forty (35%) of the 113 patients were transferred to the ICU, and 17 (15%) needed mechanical ventilation during their hospitalization. Interleukin-6 (IL-6) levels were higher in the hyponatremic group (P = .022). Intensive care unit admissions and oxygen requirement were significantly higher in hyponatremic patients (P = .001 and .016, respectively). Ferritin, lactate dehydrogenase (LDH), IL-6, total leucocyte count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were significantly elevated in those patients requiring ICU admission and those who died due to COVID-19.Conclusions:Our study revealed that demography, clinical features, radiographic findings, complications like renal insufficiency, and inflammatory markers like IL-6 play a considerable role in hyponatremic COVID-19 patients. Hyponatremia patients required significantly higher rates of ICU admissions and oxygen support. Our results suggest that monitoring inflammatory markers such as ESR, CRP, total white blood cell (WBC) count, ferritin, LDH, and IL-6 may serve as an early warning system for progression to severe COVID-19.

Treatment of Stage 3 COVID-19 With Transcutaneous Auricular Vagus Nerve Stimulation Drastically Reduces Interleukin-6 Blood Levels: A Report on Two Cases

Treatment of Stage 3 COVID-19 With Transcutaneous Auricular Vagus Nerve Stimulation Drastically Reduces Interleukin-6 Blood Levels: A Report on Two Cases

Evaluation of immunological role of Interferon gamma, Interleukin-10 and CD4+ T lymphocytes in pediatric patients with sickle cell disease

Sickle cell disease (SCD) is a chronic inflammatory disease associated with increased levels of multiple cytokines as interferon gamma (IFN-γ) during vaso-occlusive (VOC) crisis and steady state. Therefore, we aimed to explore theimmunological role of serum IFN-γ, interleukin-10 (IL-10) and CD4+ T lymphocytes in children with SCD at steady state and VOC. This study was conducted on 30 children with SCD (15 at steady state and 15 in VOC) and 30 healthy children as controls. Detailed history, complete physical, clinical examination and laboratory investigations as: complete blood count, serum ferritin, IFN-γ, IL-10 and CD4+ T lymphocytes for all patients were recorded. Results: Significant increase in serum IFN-γ in patients with SCD during VOC compared with patients at steady state and controls (P<0.001). Significant increase in serum IL-10 in patients with SCD at steady state compared with those during VOC and controls (P=0.008 and P=0.04 respectively). CD4 +T lymphocyte decreased in patients with SCD during VOC compared with those at steady state and controls (P<0.001). There was a significant positive correlation between serum IFN-ɣ and number of crisis per year (r=0.648, P=0.0001). Serum IFN-γ was increased in patients with history of frequent crisis per year (P=0.001) and decreased in patients under hydroxyurea therapy (P<0.001). IFN-γ was increased in SCD patients. Increased IFN-γ production in SCD suggesting that functionally activated natural killer cells reflecting a host immunological mechanism leading to antigen antibody activation in SCD. Serum IL-10 increased in SCD patients at steady state. CD4 +T lymphocyte decreased in patients during VOC.

Analysis of the effect of transgluteal percutaneous drainage in the treatment of deep pelvic abscess

Objective: To investigate the safety and feasibility of transgluteal percutaneous drainage using double catheterization cannula in the treatment of deep pelvic abscess. Methods: A retrospective analysis of the clinical data of patients who underwent transgluteal percutaneous drainage using double catheterization cannula with deep pelvic abscesses admitted to the Jinling Hospital from May 2017 to September 2020 was conducted. Seven patients were enrolled, including 5 males and 2 females, who aged 26-74 (median 53.0) years old, and all of them had digestive fistula. One male patient was punctured again due to the tube falling off, and a total of 7 patients underwent 8 times of transgluteal percutaneous drainage, all under the guidance of CT. The puncture and drainage steps of the double catheterization cannula group are as follows: (1) Locate the puncture point under CT in the lateral position; (2) Place the trocar into the abscess cavity; (3) Confirm that the trocar is located in the abscess cavity under CT; (4) Pull out the inner core and insert into the double catheterization cannula through the operating hole; (5) Confirmthat the double catheterization cannula is located in the abscess cavity under CT; (6) The double catheterization cannula is properly fixed to prevent it from falling off. The white blood cells, C-reactive protein (CRP), procalcitonin, and interleukin-6 (IL-6) of all patients before the drainage and 1 days, 3 days, and 5 days after the drainage were collected, as well as the bacterial culture results of the drainage fluid. The changes of various infection biomarkers before and after the drainage were compared. Results: All 7 patients were cured. No complications such as hemorrhage and severe pain were observed. The average time with drainage tube was 60.8 (18-126) days. Five patients finally underwent gastrointestinal reconstruction surgery due to gastrointestinal fistula. The median serum interleukin-6 of patients before drainage, 1 day, 3 days and 5 days after drainage were 181.6 (113.0, 405.4) μg/L, 122.2 (55.8, 226.0) μg/L, 59.2 (29.0,203.5) μg/L and 64.1 (30.0,88.4) μg/L, respectively.The level of serum interleukin-6 at 3 days and 5 days after drainage was significantly lower than before drainage (F=3.586, P=0.026). Although the white blood cell count, C-reactive protein, and procalcitonin decreased gradually after drainage compared with before drainage, the difference was not statistically significant (all P>0.05). Conclusion: Transgluteal percutaneous drainage with double catheterization cannula is simple and effective, and can be used for the treatment of deep pelvic abscess.

Significance of the ratio interferon-γ/interleukin-4 in early diagnosis and immune mechanism of unexplained recurrent spontaneous abortion.

To investigate the significance of T helper type 1 (Th1)/Th2 cytokines in the pathogenesis of unexplained recurrent spontaneous abortion (URSA), and reveal the value of single cytokines and their proportions in early diagnosis. A total of 44 URSA patients (URSA group), 51 patients with adverse pregnancy history (ad-pregnancy group), and 42 healthy volunteers with normal pregnancy (pregnancy group) were recruited for a cross-sectional study from July 2018 to April 2019 in the Second Xiangya Hospital. Pregnancies involving chromosomal abnormalities, infection, autoimmune diseases, and anatomical abnormalities were excluded. Flow cytometry was used to determine the level of Th1/Th2 cytokines in peripheral blood. The level of interleukin-6 (IL-6) in the peripheral blood of the ad-pregnancy group was significantly higher than in the other two groups. The ratio of interferon-γ (IFN-γ)/IL-4 in the URSA group was significantly higher than that of the pregnancy group. The area under the curve for IFN-γ/IL-4 was 0.821, with high diagnostic efficiency, and sensitivity as high as 84.09%. Laboratory testing for IL-6 is not recommended for the diagnosis or monitoring of URSA. The variable IFN-γ/IL-4 can be used for the initial diagnosis of URSA to reduce the rate of missed diagnosis. This ratio was more important than the expression of a single cytokine in the Th1/Th2 immune response.

Hyperglycemia associated with lymphopenia and disease severity of COVID-19 in type 2 diabetes mellitus.

BackgroundCoronavirus disease 2019 (COVID-19) has been declared a global pandemic. COVID-19 is more severe in people with diabetes. The identification of risk factors for predicting disease severity in COVID-19 patients with type 2 diabetes mellitus (T2DM) is urgently needed.MethodsTwo hundred and thirty-six patients with COVID-19 were enrolled in our study. The patients were divided into 2 groups: COVID-19 patients with or without T2DM. The patients were further divided into four subgroups according to the severity of COVID-19 as follows: Subgroup A included moderate COVID-19 patients without diabetes, subgroup B included severe COVID-19 patients without diabetes, subgroup C included moderate COVID-19 patients with diabetes, and subgroup D included severe COVID-19 patients with diabetes. The clinical features and radiological assessments were collected and analyzed. We tracked the dynamic changes in laboratory parameters and clinical outcomes during the hospitalization period. Multivariate analysis was performed using logistic regression to analyze the risk factors that predict the severity of COVID-19 with T2DM.ResultsFirstly, compared with the nondiabetic group, the COVID-19 with T2DM group had a higher erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and procalcitonin (PCT) but lower lymphocyte counts and T lymphocyte subsets, including CD3+ T cells, CD8+ T cells, CD4+ T cells, CD16 + CD56 cells, and CD19+ cells. Secondly, compared with group A, group C had higher levels of Fasting blood glucose (FBG), IL-6, TNF-α, and neutrophils but lower lymphocyte, CD3+ T cell, CD8+ T cell, and CD4+ T cell counts. Similarly, group D had higher FBG, IL-6 and TNF-α levels and lower lymphocyte, CD3+ T cell, CD8+ T cell, and CD4+ T cell counts than group B. Thirdly, binary logistic regression analysis showed that HbA1c, IL-6, and lymphocyte count were risk factors for the severity of COVID-19 with T2DM. Importantly, COVID-19 patients with T2DM were more likely to worsen from moderate to severe COVID-19 than nondiabetic patients. Of note, lymphopenia and inflammatory responses remained more severe throughout hospitalization for COVID-19 patients with T2DM.ConclusionOur data suggested that COVID-19 patients with T2DM are more likely to develop severe COVID-19 than those without T2DM and that hyperglycemia associated with the lymphopenia and inflammatory responses in COVID-19 patients with T2DM.

Inflammatory-Related Clinical and Metabolic Outcomes in COVID-19 Patients.

Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection elicits inflammatory manifestations that relate with a “cytokine storm.” Objective The aim of this research was to assess the role of circulating interleukin 6 (IL-6) levels and other inflammatory markers in patients with coronavirus disease 2019 (COVID-19) on metabolic functions and accompanying clinical complications. Patients and Methods. A total of 165 patients diagnosed with COVID-19 pneumonia were examined for medical features and inflammatory markers such as blood IL-6, CRP, ferritin, LDH, neutrophil/lymphocyte index (NLI), D-Dimer, and Red Cell Distribution Width (RDW). Regression analyses concerning electronically collected medical data were adjusted by appropriate factors and confounding variables. Results. Plasma IL-6 determinations evidenced a consistent association with hospital stay days, Intensive Care Unit (ICU) admission, and mortality rates. Similar trends were found for other proinflammatory variables, where ferritin and NLI showed a remarkable value as surrogates. Hyperglycaemia and the Charlson Comorbidity Index Score were positively associated with the inflammatory response induced by the SARS-COV-2 infection. An unhealthy lifestyle such as smoking and alcoholic drinks consumption as well as excessive body adiposity influenced inflammatory-related outcomes in the screened patients. Conclusion IL-6 together with other inflammatory biomarkers accompanied poor clinical and metabolic outcomes in COVID-19-infected patients. IL-6 may result in a suitable proxy to individually categorise patients in order to manage this infectious pandemic.

Changes in Peripheral Blood Neutrophils, Lymphocytes and IL-10 in Children with Kawasaki Disease from Different Age Groups Undergoing Intravenous Immunoglobulin: A Retrospective Study.

Immunoglobulin intravenous (IVIG) is widely used in mucocutaneous lymph node syndrome, known as Kawasaki disease (KD). However, the patients' inflammatory response during usage remains unclear. In the present study, the association between inflammatory response and lymphocyte count in children with KD from different ages was evaluated before and after IVIG. The medical records of 50 children with KD were retrospectively reviewed and divided into five groups according to age. As compared with the data from healthy children, the relative neutrophil count of all children with KD was increased, and that of lymphocytes was decreased. The neutrophil/lymphocyte ratio (NLR) was different among all groups and was higher in children aged ≥4 years, as compared with other groups. Following IVIG, the relative neutrophil and lymphocyte counts of all children with KD returned to normal levels. The altered levels of neutrophils and lymphocytes were found to be linearly correlated. The correlation coefficient in the five groups was 0.99, 0.87, 0.91, 0.97 and 0.99, from young to old, respectively (p < 0.01). The age of children with KD was positively correlated with older age (r = 0.91, p = 0.03). In patients aged ≥4 years, the absolute CD19+ B cell count prior to IVIG increased, and that increase was linearly correlated with the decrease in interleukin-10 (IL-10) following IVIG (r = 0.71, p < 0.05). The older the child's age, the better the regulatory effect of IVIG on the KD child's immune response and the recovery of immune equilibrium it achieved. In KD patients aged ≥4 years, the abnormally proliferating CD19+ B cells may be involved in the secretion of IL-10 to balance the humoral immunity. In such patients, the combination of the absolute CD19+ B cell count prior to IVIG and the decreased levels of IL-10 following IVIG may play a crucial role in evaluating the effect of IVIG in the inflammation.

Impact of Coffee Consumption on Physiological Markers of Cardiovascular Risk: A Systematic Review

BackgroundCoffee is one of the most widely consumed beverages globally. A substantial number of observational data suggest an inverse relationship between coffee consumption and the risk for cardiovascular disease. The basis for this association is not clear. In this review, we specifically study the impact of coffee on inflammatory biomarkers as one potential mechanistic basis for this observation. Our objective was to systematically review randomized controlled trials that examined the effects of coffee consumption on selected cardiovascular biomarkers. MethodsWe systematically reviewed bibliographic databases including PubMed (NCBI), Embase (Elsevier), CINAHL (EBSCO), Web of Science (Clarivate Analytics), Cochrane Central Register of Controlled Trials (EBSCO), and CAB Abstracts (Clarivate Analytics). We searched for randomized controlled trials that studied the effect of drinking coffee on inflammatory markers of cardiovascular risk. ResultsThe search of electronic databases returned 1631 records. After removing duplicate records and ineligible studies, we examined a total of 40 full-text documents, 17 of which were eligible for further analysis. In our review, boiled coffee, in particular, appeared to raise total and low-density lipoprotein cholesterol and apolipoprotein B, but evidence suggests no similar effect for filtered coffee. One study showed a significant increase in blood interleukin 6 levels among individuals who drank caffeinated coffee, compared with individuals consuming no coffee. ConclusionBased on our systematic review of randomized controlled studies, we cannot confidently conclude that an anti-inflammatory effect of coffee is a major contributing factor to the lower all-cause mortality reported in observational studies.