Including Interleukin-6 Levels Research Articles

Diagnostic value and correlation analysis of serum cytokine levels in patients with multiple system atrophy.

The association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA. Serum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves. No significant differences were found in sex and age between the MSA group and the HCs. TNF-α in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-α in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-α, and only HAMA was mild related with IL-6 levels in MSA patients. Serum TNF-α and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-α was shown to be a useful tool in distinguishing between MSA and HCs.

Tocilizumab unfolds colo-protective and immunomodulatory effect in experimentally induced ulcerative colitis via mitigating autophagy and ER stress signaling

Ulcerative colitis (UC) is an idiopathic, chronic, relapsing inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. The pathophysiology of UC is complicated and involves several factors including immune, genetic, and environmental factors. Recently, a huge amount of research has concentrated on the role of interleukins including interleukin-6 (IL-6) in its pathophysiology. Thus, this study aims to examine the colo-protective and immunomodulatory effect of Tocilizumab (TCZ) in an experimental model of dextran sulfate sodium (DSS) induced UC. In the current study, we analyzed the inflammatory, immunomodulatory, apoptotic, autophagy, and endoplasmic reticulum (ER) stress markers and other clinical features including stool consistency, rectal bleeding, and edema markers in rats. Our results showed that induction of colitis caused bloody diarrhea and increased IL-6 levels. Treatment with TCZ significantly ameliorated DSS-induced injury via decreasing inflammatory markers of colon injury (IL-6), signal transducer and activator of transcription-3 (STAT-3), and C-reactive protein (CRP). Furthermore, TCZ attenuated the apoptotic marker (caspase-3), and down-regulated endoplasmic reticulum stress sensor proteins (inositol- requiring transmembrane kinase endonuclease-1 (IRE-1) and activated transcription factor-6 (ATF-6)) and autophagy proteins (autophagy-related 16-like protein 1 (ATG16L1) and nucleotide-binding oligomerization domain-containing protein-2 (NOD2)), as compared to DSS group. Altogether, the current data suggest TCZ to be a promising protective therapy against UC.Graphical

Effects of an 8-week high-dose vitamin D supplementation on fatigue and neuropsychiatric manifestations in post-COVID syndrome: A randomized controlled trial.

This study evaluated the effectiveness of high-dose vitamin D supplementation in alleviating fatigue and neuropsychiatric symptoms in post-COVID syndrome. In an 8-week, double-blind, randomized, placebo-controlled trial, 80 patients with post-COVID fatigue or neuropsychiatric symptoms were enrolled. Participants were randomly assigned to receive either 60,000 IU of vitamin D weekly (n = 40) or a placebo (n = 40) for 8 weeks. Clinical outcomes were assessed using the 11-item Chalder Fatigue Scale (CFQ-11); 21-item Depression, Anxiety, and Stress Scale (DASS-21); Pittsburgh Sleep Quality Index (PSQI); Addenbrooke's Cognitive Examination III (ACE); and Trail Making Test A and B (TMT-A and TMT-B). Baseline and 8-week measurements of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also collected. Significant improvements were found in the vitamin D group for CFQ (coefficient -3.5, P = 0.024), DASS-anxiety (-2.0, P = 0.011), and ACE (2.1, P = 0.012). No significant differences were observed in PSQI, DASS-depression, TMT, IL-6, or CRP levels. The incidence of adverse events was comparable between groups, with no serious adverse events reported. High-dose vitamin D supplementation may benefit patients with post-COVID syndrome by reducing fatigue, alleviating anxiety, and improving cognitive symptoms, with minimal side effects.

Diagnostic Value of Interleukin 6, Interleukin 12P70, Serum Amyloid A, and Procalcitonin for Rheumatoid Arthritis and Their Relationship With the Disease Activity

To observe the diagnostic value of four serum inflammatory biomarkers, including interleukin 6 (IL-6), interleukin 12P70 (IL-12P70), serum amyloid A (SAA), and procalcitonin (PCT), in rheumatoid arthritis (RA) and to analyze their relationship with the disease activity. The study included 60 RA patients admitted to the Department of Rheumatology at Anhui Provincial Hospital of Traditional Chinese Medicine between December 2022 and December 2023. Thirty healthy individuals from the hospital's physical examination center served as the control group. Serum levels of IL-6 and IL-12P70 were detected using flow cytometry. SAA levels were determined by immunoturbidimetry, and PCT levels were assessed by chemiluminescence. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated peptide (ACCP) were detected using an automated biochemical analyzer. The 28-joint disease activity scores (DAS28-ESR) based on ESR were observed. Statistical analysis included t-tests, rank-sum tests, and Kruskal-Wallis H tests to compare the expression differences of the biomarkers among different groups. The diagnostic value of these biomarkers for RA was analyzed by ROC curve analysis. Spearman correlation analysis was performed to assess the relationships between the four inflammatory biomarkers and CRP, ESR, RF, ACCP, and DAS28-ESR. 1) The expression levels of SAA, IL-6, and IL-12P70 in the RA group were significantly higher than those in the control group (P<0.01). 2) ROC curve analysis showed that the area under the curve (AUC) for PCT was 0.611 (95% confidence interval [CI]: 0.488-0.735, P>0.05), for SAA, it was 0.819 (95% CI: 0.733-0.906, P<0.01), for IL-6, it was 0.875 (95% CI: 0.803-0.946, P<0.01), and for IL-12P70, it was 0.832 (95% CI: 0.746-0.917, P<0.01). The combined index of IL-6, IL-12P70, SAA, and PCT had an AUC of 0.973 (95% CI: 0.942-1.000, P<0.01). This indicates that the four inflammatory biomarkers can assist in the diagnosis of rheumatoid arthritis. 3) The expression levels of PCT and SAA varied significantly among the high, moderate, and low activity RA groups (P<0.01). 4) In RA patients, CRP was positively correlated with SAA (rs =0.75, P<0.01), and IL-6 (rs =0.52, P<0.01). ESR was positively correlated with SAA (rs =0.36, P<0.01). DAS28-ESR was positively correlated with PCT (rs =0.34, P=0.01), SAA (rs =0.51, P<0.01) and IL-6 (rs =0.33, P=0.01). The four inflammatory biomarkers (PCT, SAA, IL-6, and IL-12P70) are closely related to rheumatoid arthritis disease activity and can serve as serum indicators to assist in the diagnosis and assessment of RA.

Scutellarein Suppresses the Production of ROS and Inflammatory Mediators of LPS-Activated Bronchial Epithelial Cells and Attenuates Acute Lung Injury in Mice.

Scutellarein is a key active constituent present in many plants, especially in Scutellaria baicalensis Georgi and Erigeron breviscapus (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative activities. It also is the metabolite of scutellarin, with the ability to relieve LPS-induced acute lung injury (ALI), strongly suggesting that scutellarein could suppress respiratory inflammation. The present study aimed to investigate the effects of scutellarein on lung inflammation by using LPS-activated BEAS-2B cells (a human bronchial epithelial cell line) and LPS-induced ALI mice. The results showed that scutellarein could reduce intracellular reactive oxygen species (ROS) accumulation through inhibiting the activation of NADPH oxidases, markedly downregulating the transcription and translation of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand (CXCL) 8 in LPS-activated BEAS-2B cells. The mechanism study revealed that it suppressed the phosphorylation and degradation of IκBα, consequently hindering the translocation of p65 from the cytoplasm to the nucleus and its subsequent binding to DNA, thereby decreasing NF-κB-regulated gene transcription. Notably, scutellarein had no impact on the activation of AP-1 signaling. In LPS-induced ALI mice, scutellarein significantly decreased IL-6, CCL2, and tumor necrosis factor-α (TNF-α) levels in the bronchoalveolar lavage fluid, attenuated lung injury, and inhibited neutrophil infiltration. Our findings suggest that scutellarein may be a beneficial agent for the treatment of infectious pneumonia by virtue of its anti-oxidative and anti-inflammatory activities.

Interleukin 6 at menstruation promotes the proliferation and self-renewal of endometrial mesenchymal stromal/stem cells through the WNT/β-catenin signaling pathway.

At menstruation, the functional layer of the human endometrium sheds off due to the trigger of the release of inflammatory factors, including interleukin 6 (IL-6), as a result of a sharp decline in progesterone levels, leading to tissue breakdown and bleeding. The endometrial mesenchymal stem-like cells (CD140b+CD146+ eMSC) located in the basalis are responsible for the cyclical regeneration of the endometrium after menstruation. Endometrial cells from the menstruation phase have been proven to secrete a higher amount of IL-6 and further enhance the self-renewal and clonogenic activity of eMSC. However, the IL-6-responsive mechanism remains unknown. Thus, we hypothesized that IL-6 secreted from niche cells during menstruation regulates the proliferation and self-renewal of eMSC through the WNT/β-catenin signaling pathway. In this study, the content of IL-6 across the menstrual phases was first evaluated. Coexpression of stem cell markers (CD140b and CD146) with interleukin 6 receptor (IL-6R) was confirmed by immunofluorescent staining. In vitro functional assays were conducted to investigate the effect of IL-6 on the cell activities of eMSC, and the therapeutic role of these IL-6- and WNT5A-pretreated eMSC on the repair of injured endometrium was observed using an established mouse model. The endometrial cells secrete a high amount of IL-6 under hypoxic conditions, which mimic the physiological microenvironment in the menstruation phase. Also, the expression of IL-6 receptors was confirmed in our eMSC, indicating their capacity to respond to IL-6 in the microenvironment. Exogenous IL-6 can significantly enhance the self-renewal, proliferation, and migrating capacity of eMSC. Activation of the WNT/β-catenin signaling pathway was observed upon IL-6 treatment, while suppression of the WNT/β-catenin signaling impaired the stimulatory role of IL-6 on eMSC activities. IL-6- and WNT5A-pretreated eMSC showed better performance during the regeneration of the injured mouse endometrium. We demonstrate that the high level of IL-6 produced by endometrial cells at menstruation can induce the stem cells in the human endometrium to proliferate and migrate through the activation of the WNT/β-catenin pathway. Treatment of eMSC with IL-6 and WNT5A might enhance their therapeutic potential in the regeneration of injured endometrium.

β-Nicotinamide Mononucleotide Promotes Cell Proliferation and Hair Growth by Reducing Oxidative Stress.

β-Nicotinamide mononucleotide (NMN) has shown promising effects on intestinal health, and it is extensively applied as an anti-aging and Alzheimer's disease therapeutic, due to its medicinal properties. The effects of NMN on the growth of mouse hair were observed after hair removal. The results indicated that NMN can reverse the state of hair follicle atrophy, hair thinning, and hair sparsity induced by dihydrotestosterone (DHT), compared to that of minoxidil. In addition, the action mechanisms of NMN promoting hair growth in cultured human dermal papilla cells (HDPCs) treated with DHT were investigated in detail. The incubation of HDPCs with DHT led to a decrease in cell viability and the release of inflammatory mediators, including interleukin-6 (IL-6), interleukin-1Beta (IL-1β) and tumor necrosis factor Alpha (TNF-α). It was found that NMN can significantly lower the release of inflammatory factors induced by DHT in HDPCs. HDPCs cells are protected from oxidative stress damage by NMN, which inhibits the NF-κB p65 inflammatory signaling pathway. Moreover, the levels of androgen receptor (AR), dickkopf-1 (DKK-1), and β-catenin in the HDPCs were assessed using PCR, indicating that NMN can significantly enhance the expression of VEGF, reduced IL-6 levels and suppress the expression of AR and DKK-1, and notably increase β-catenin expression in DHT-induced HDPCs.

Role of IL-6 as ‘core inflammatory marker’ in assessment of severity, response to therapy and predicting outcome in COVID-19 pneumonia: A single center experience of 2400 cases in tertiary care setting in India

Objectives: In coronavirus disease-19 (COVID-19) pneumonia, the role of various inflammatory markers including interleukin-6 (IL-6) was evolved in managing cases in indoor or critical care units worldwide. Apart from the role of IL-6 in predicting cytokine storms, the role in assessing post-COVID outcome is less studied. In the present study, we have analyzed the role in predicting ventilatory support requirement and final outcome in COVID-19 pneumonia. Material and Methods: A prospective, observational, and 12 weeks follow-up study included 2400 COVID-19 cases confirmed with reverse transcription-polymerase chain reaction. All cases were assessed with lung involvement documented and categorized on high-resolution computerized tomography (HRCT) thorax, oxygen saturation (SpO2), and IL-6 at entry point and follow-up. Covariates such as age, gender, and comorbidity; interventions such as oxygen use, bi-level positive airway pressure/non-invasive ventilation (BIPAP/NIV); and timings of ventilatory support and final outcome as with or without lung fibrosis as per computed tomography severity were recorded. Covariates were analyzed with initial and sequential IL-6 titer. Statistical analysis is done by Chi-square test. Results: The study of 2400 COVID-19 pneumonia cases, age (&lt;50 and &gt;50 years), gender, and comorbidity has a significant association with IL-6 titer (P &lt; 0.00001). HRCT severity score at entry point and duration of illness has a significant correlation with IL-6 level (P &lt; 0.00001). IL-6 titer has a significant association with SpO2 and BIPAP/NIV requirement during hospitalization (P &lt; 0.00001). Timing of BIPAP/NIV requirement during the course of hospitalization in the intensive care unit has a significant association with IL-6 titer (P &lt; 0.00001). Follow-up IL-6 titer during hospitalization as compared to entry point normal and abnormal IL-6 has a significant association in post-COVID lung fibrosis (P &lt; 0.00001). Follow-up IL-6 titer during hospitalization as compared to entry point abnormal IL-6 has a significant association in predicting cytokine storms irrespective of normal or abnormal IL-6 at entry point (P &lt; 0.0001). Conclusion: IL-6 titer has documented a very important role in triaging the COVID-19 pneumonia cases in indoor units, and guided treatments have shown improved outcomes. IL-6 titer is the “game changer” inflammatory marker not only in assessing the severity or predicting course during hospitalization but it has also helped in the utilizations of timely interventions required during hospitalizations. Sequential IL-6 titer has shown a significant role in predicting final radiological outcomes at 12 weeks.

The effects of alfacalcidol combined with calcitonin in the treatment of osteoporosis and its influence on levels of inflammation.

To investigate the effectiveness of Alfacalcidol combined with Calcitonin in the treatment of osteoporosis and its influence on the degree of pain, bone metabolism indexes, bone mineral density and inflammatory factor levels. In this retrospective study, 110 patients with osteoporosis treated in The Second Affiliated Hospital of Shandong First Medical University from January 2019 to June 2021 were selected as the study subjects. According to different treatment methods, these patients were divided into an observation group and a control group with 55 cases in each group. Patients from the control group were treated with the alfacalcidol capsules alone, while those from the observation group were treated with the alfacalcidol capsules combined with intramuscular calcitonin injection. Patients in both groups were treated for 6 months continuously. The treatment effect, visual analogue scale (VAS) score and Oswestry disability index (ODI), bone mineral density (BMD), serum markers levels such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase-5b (TRACP-5b), insulin-like growth factor (IGF-1), type I procollagen amino terminal propeptide (PINP) and β-collagen special sequence (β-Crosslaps), the levels of inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), quality Life Questionnaire Core 30 (QLQ-C30) scores and incidences of adverse reactions were evaluated and compared between the two groups. The effective rate of patients in the observation group was 90.91%, which was significantly higher than 74.54% in the control group (P<0.05). There was no significant difference in the term of VAS score, ODI score, serum markers levels, bone mineral density, inflammatory levels, QLQ-C30 before treatment between the two groups. Compared with the control group, the post-treatment VAS score, ODI score, the levels of IL-6, TNF-α, TRACP-5b, PINP and β-Crosslaps in the observation group were obviously lower, while the post-treatment QLQ-C30, bone mineral density, Ca, P, ALP, IGF-1 levels were significantly higher (all P<0.05). No statistical differences were found in the incidences of adverse reactions between the two groups (P>0.05). The combination of Alfacalcidol combined with Calcitonin is effective in the treatment of osteoporosis patients, which can effectively improve the levels of bone metabolism indexes and bone mineral density, alleviate the symptoms, enhance the life quality and reduce the levels of inflammation. Therefore, it is worth promoting.

Minocycline hydrochloride plus metronidazole versus metronidazole alone for peri-implantitis: a comparative study.

To evaluate the efficacy of minocycline hydrochloride combined with metronidazole versus metronidazole alone in treating peri-implantitis and their impact on specific inflammatory markers. A retrospective review was undertaken of 107 patients with peri-implantitis from January 2018 to January 2021. Patients were treated either with metronidazole alone (Con group, n = 57) or with additional minocycline hydrochloride (Exp group, n = 50). Inflammatory markers, including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase-8 (MMP-8) were determined before and after treatment. Clinical outcomes were determined using the plaque index (PLI), gingival sulcus bleeding index (SBI), and periodontal probing depth (PD). Furthermore, receiver operator characteristic (ROC) curves analyzed the clinical relevance of the markers. Logistic regression was conducted to analyze the risk factors affecting efficacy in patients. The Exp group exhibited more favorable clinical outcomes and showed lower levels of IL-6, IL-1β, TNF-α, and MMP-8 than the Con group. IL-1β, TNF-α, and MMP-8 levels were significantly correlated with treatment success (P < 0.05), but IL-6 was not (P > 0.05). The ROC curves for IL-1β and TNF-α significantly outperformed those for IL-6 and MMP-8 (P < 0.05). Logistic regression analysis showed that only IL-1β and TNF-α were independent risk factors affecting efficacy in patients. Combining minocycline hydrochloride with metronidazole yields better outcomes for peri-implantitis compared to metronidazole alone. Of the factors analyzed, only IL-1β and TNF-α emerged as dependable independent efficacy indicators.

Review of Decreased IL-6 Levels in SOPK-Insulin Resistant Rats fed a Low Carb High Protein Diet

Polycystic ovary syndrome with insulin resistance (SOPK-RI) is caused among endocrine disorders with an incidence rate of 5-10% that occurs in women of reproductive age. Characteristics of polycystic ovary syndrome are found anovulation, hyperandrogens, polycystic ovarii and impaired insulin sensitivity involving proinflammatory increases in several inflammatory cytokines including interleukin-6 (IL-6). Increased inflammatory cytokines in women with SOPK-RI found health problems there is fat accumulation in adipocyte tissue such as in an obese person, metabolic syndrome and type 2 diabetes. The purpose of this study was to determine the effect of a low-carbohydrate high-protein diet on changes in IL-6 levels in SOPK-RI model mice. Laboratory experimental research, namely post test only control group design. Consisting of three groups, namely, the negative control group (K-) as a normal group did not get treatment; The positive control group (K+) of the SOPK-insulin resistance model mice were given standard feed, and the treatment group (P) of the SOPK-insulin resistance model mice were given a low-carbohydrate high-protein diet (CTR) with a composition of 40% carbohydrate and 30% protein. The study lasted for 48 days, using serum ELISA examination on IL-6 levels. The average results of IL-6 levels, namely the K- = 0.358 group, K+ = 0.387 and P = 0.442 and obtained different IL-6 levels of significance value p = 0.002 with a low-carbohydrate high-protein diet in SOPK - RI rats showed a significant difference (p &lt; 0.05) between the control group and the treatment group. Significantly reduced IL-6 levels in SOPK-RI model mice. A low-carb, high-protein diet may be considered as a dietary modality in women with SOPK-insulin resistance. Further research is needed to better determine the other modulators involved in this mechanism in more detail.

Prenatal immobility stress: Relationship with oxidative stress, inflammation, apoptosis, and intrauterine growth restriction in rats.

Prenatal stress is a significant risk factor affecting pregnant women and fetal health. In the present study, we aimed to investigate the effect of immobility stress at different periods of pregnancy on oxidative stress, inflammation, placental apoptosis and intrauterine growth retardation in rats. Fifty adult virgin female Wistar albino rats were used. Pregnant rats were exposed to 6 h/day immobilization stress in a wire cage at different stages of pregnancy. Groups I and II (Day 1-10 stress group) were sacrificed on the 10th day of pregnancy, and Group III, Group IV (10-19th-day stress group), and Group V (1-19th-day stress group) were sacrificed on the 19th day of pregnancy. Inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-10 (IL-10), serum corticotropin-releasing hormone (CRH), and corticosterone levels were measured by enzyme-linked immunosorbent assay. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the placenta were spectrophotometrically measured. Histopathological analyses of the placenta were evaluated by hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivity in placenta tissues were determined by the indirect immunohistochemical method. Placental apoptosis was determined by the TUNEL staining method. We found that the immobility stress during pregnancy significantly increased serum corticosterone levels. Our results showed that the immobility stress diminished the number and weight of fetuses in rats compared to the non-stress group. The immobility stress caused significant histopathological changes in the connection zone and labyrinth zone and increased placental TNF-α and caspase-3 immunoreactivity and placental apoptosis. In addition, immobility stress significantly increased the levels of pro-inflammatory IL-6 and MDA and caused a significant decrease in the levels of antioxidant enzymes such as SOD, CAT, and anti-inflammatory IL-10. Our data suggest that immobility stress causes intrauterine growth retardation by activating the hypothalamic-pituitary-adrenal axis and deteriorating placental histomorphology and deregulating inflammatory and oxidative processes.

Resolution of elevated interleukin-6 after surgery is associated with return of normal cognitive function

BackgroundUnresolved surgical inflammation might induce chronic cognitive decline in older adults. Although inflammatory biomarkers have been correlated with perioperative cognitive impairment and delirium, the effects of prolonged inflammation on cognition are not well studied. This prospective cohort study investigated 1-yr dynamics in plasma interleukin-6 levels and executive function. MethodsPatients undergoing major surgery (n=170) aged ≥65 yr completed Trail Making Test B and other neuropsychological assessments with plasma interleukin-6 levels collected on postoperative days 1–9 and 90, and at 1-yr. Mixed-effects analyses were conducted for Trail Making Test B (and other assessments), including interleukin-6 levels, time, and additional confounders (fixed effects), and a random effect for participant. ResultsChanges in interleukin-6 levels were associated with changes in Trail Making Test B over 1 yr in a generalised additive model (β=0.074, P<0.001) supporting that unresolved inflammation impaired executive function. This result was robust to confounders, outlier rejection, and fitting to non-linear models. Changes in interleukin-6 levels also correlated with changes in Trail Making Test A and Controlled Oral Word Association Test. Sensitivity analyses conducted on binary definitions of cognitive decline (>1, >1.5, or >2 standard deviations from baseline) were also associated with interleukin-6 changes. ConclusionsDelayed resolution of inflammation is associated with cognitive impairment after surgery. Monitoring interleukin-6 might provide an opportunity to intervene with anti-inflammatory therapies in vulnerable patients. Clinical trial registrationNCT01980511, NCT03124303.

Abrusamide H Impairs the Secretion of the Cytokines in RAW264.7 Cells and the Inflammatory Infiltration in Tail Transection-Induced Zebrafish.

Abrus mollis Hance (Leguminosae) has a variety of biological activities, including anti-inflammatory, antioxidant, antibacterial, antiviral, and antitumor activities. However, the specific substances responsible for the anti-inflammatory effects are unknown. Abrusamide H (BJBS) is a truxillic acid derivative obtained from the leaves of Abrus mollis Hance and has potential anti-inflammatory effects. In this study, we aimed to estimate the potential effect and mechanism of BJBS in inflammation by establishing lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro and an injured zebrafish tail fin in vivo. The RAW264.7 cells were treated with different concentrations of BJBS after LPS stimulation. The production of nitric oxide (NO) was detected by Griess reaction, and reactive oxygen species (ROS) were detected by an ROS assay kit. The levels of proinflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 18 (IL-18) were measured by ELISA. Results showed that BJBS at all concentrations inhibited the proliferation of RAW264.7 macrophages after LPS stimulation by cell counting kit-8 and the production of NO and ROS. In the BJBS treatment group, the levels of IL-6, TNF-α, IL-1β, and IL-18 decreased in a concentration-dependent manner. The results in vivo showed that no significant difference in the survival of zebrafish between the BJBS and blank groups and BJBS inhibited the migration and aggregation of zebrafish neutrophils in a dose-dependent manner in inflammation induced by tail transection-induced inflammation. In conclusion, BJBS inhibited the production of NO and ROS, decreased the levels of secreted IL-6, TNF-α, IL-1β, and IL-18, and reduced the migration and aggregation of zebrafish neutrophils.

Vegetable glycerin e-cigarette aerosols cause airway inflammation and ion channel dysfunction.

Vegetable glycerin (VG) and propylene glycol (PG) serve as delivery vehicles for nicotine and flavorings in most e-cigarette (e-cig) liquids. Here, we investigated whether VG e-cig aerosols, in the absence of nicotine and flavors, impact parameters of mucociliary function in human volunteers, a large animal model (sheep), and air-liquid interface (ALI) cultures of primary human bronchial epithelial cells (HBECs). We found that VG-containing (VG or PG/VG), but not sole PG-containing, e-cig aerosols reduced the activity of nasal cystic fibrosis transmembrane conductance regulator (CFTR) in human volunteers who vaped for seven days. Markers of inflammation, including interleukin-6 (IL6), interleukin-8 (IL8) and matrix metalloproteinase-9 (MMP9) mRNAs, as well as MMP-9 activity and mucin 5AC (MUC5AC) expression levels, were also elevated in nasal samples from volunteers who vaped VG-containing e-liquids. In sheep, exposures to VG e-cig aerosols for five days increased mucus concentrations and MMP-9 activity in tracheal secretions and plasma levels of transforming growth factor-beta 1 (TGF-β1). In vitro exposure of HBECs to VG e-cig aerosols for five days decreased ciliary beating and increased mucus concentrations. VG e-cig aerosols also reduced CFTR function in HBECs, mechanistically by reducing membrane fluidity. Although VG e-cig aerosols did not increase MMP9 mRNA expression, expression levels of IL6, IL8, TGFB1, and MUC5AC mRNAs were significantly increased in HBECs after seven days of exposure. Thus, VG e-cig aerosols can potentially cause harm in the airway by inducing inflammation and ion channel dysfunction with consequent mucus hyperconcentration.

Study on the concentration of serum interleukin-6 in rheumatoid arthritis patients

Background: Helper T lymphocytes 17 (Th17) secrete various interleukins, including Interleukin-6 (IL-6), which promotes the pathological process in rheumatoid arthritis patients. Therefore, serum Interleukin-6 levels may be related to the clinical and subclinical characteristics of rheumatoid arthritis. Objectives: To determine serum Interleukin-6 concentrations in rheumatoid arthritis patients and to investigate the relationship between serum Interleukin-6 concentration with some clinical and subclinical characteristics in patients with rheumatoid arthritis. Subjects and method: A cross-sectional descriptive study of 41 patients with rheumatoid arthritis in Hue University of Medicine and Pharmacy hospital and 30 healthy people in a control group. Results: The mean serum IL-6 concentration of the patient group was 120.57 pg/mL which was statistically significantly higher (p &lt; 0.001) than the control group (5.73 pg/mL). There was a statistically significant positive correlation (p &lt; 0.05) between serum Interleukin-6 concentration and the time of disease onset, the number of damaged joints and the 2nd-hour erythrocyte sediment rate. There was a statistically significant inverse correlation (p &lt; 0.05) between serum Interleukin-6 concentration with red blood cell amount, hemoglobin concentration. There was a statistically significant relationship (p &lt; 0.05) between serum Interleukin-6 concentration and CRP, RF, Anti-CCP and 1st-hour erythrocyte sediment rate. Conclusion: Increased serum IL-6 levels in rheumatoid arthritis patients affect joint injury, induce anemia, promote inflammation and increase autoantibodies. Key words: Interleukin-6, Rheumatoid Arthritis.

Effect of dexmedetomidine administration on analgesic, respiration and inflammatory responses in patients undergoing percutaneous endoscopic lumbar discectomy: a prospective observational study

BackgroundLocal anesthesia has been recommended for percutaneous endoscopic lumbar discectomy (PELD) in recent years; however, the efficacy, including oxidative stress, inflammatory reactions and ventilation effects, when intravenous dexmedetomidine (DEX) is administered during PELD has not been described.MethodsSixty adult patients undergoing PELD were randomly allocated to either an intravenous DEX sedation group (Group A) or a normal saline group (Group B). Respiratory data, including minute ventilation (MV), tidal volume (TV), and respiratory rate (RR), were recorded using a respiratory volume monitor (RVM), and peripheral oxygen saturation (SpO2) was monitored by pulse oximetry. The visual analog score (VAS) was used to assess the level of pain. The serum levels of inflammatory biomarkers including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were to assess inflammatory reactions. The serum levels of oxidative stress biomarkers including malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were also recorded to evaluate oxidative stress.ResultsThere were no significant differences in RR, MV, TV and SpO2 between the two groups at any time point (P > 0.05). Group B exhibited lower serum levels of GSH-PX (P < 0.0001) and higher serum levels of MDA (p < 0.0001) than Group A at the end of surgery. Twenty-four hours after surgery, Group B exhibited higher serum levels of IL-6 (P = 0.0033), TNF-α (P = 0.0002), and MDA (P < 0.0001) and lower serum levels of GSH-PX (P < 0.0001) than Group A. In addition, Group A exhibited lower VAS (P < 0.0001) than Group B during surgery.ConclusionsDEX administration using RVM not only provides analgesia without ventilatory depression but also alleviates oxidative stress and inflammatory reactions in patients undergoing PELD.

Relationships between sodium levels, haemodynamics and metalloproteinases in heart failure patients.

To estimate the associations between dysnatraemia and inflammatory marker [including interleukin-6 (IL-6)], and tissue remodelling marker [matrix metalloproteinase (MMP)-9 and tissue inhibitor of MMP (TIMP)-1], the pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure (PAP), and left ventricular end-diastolic pressure (EDP), and the prognostic relevance in patients with heart failure. The serum sodium level and circulating levels of IL-6, MMP-9, and TIMP-1 were measured in 173 heart failure patients. Dual heart catheterisation was performed to measure PCWP, mean PAP, and EDP. All-cause mortality was assessed during the follow-up period (mean 88 ± 49months). Restricted cubic spline (RCS) regression showed a U-shaped association of serum sodium level with TIMP-1, with the lowest values in the 138-140mmol/L range (P for effect = 0.042, P for non-linearity = 0.017). IL-6 and MMP-9 levels showed non-significant associations with serum sodium level. U-shaped associations of serum sodium level with PCWP (P for effect = 0.004, P for non-linearity = 0.001) and mean PAP (P for effect = 0.042, P for non-linearity = 0.017) were found with the RCS regression model. The random forest model revealed that TIMP-1, MMP-9, and IL-6 were important predictors for serum sodium levels. Restricted cubic spline Cox regressions demonstrated that TIMP-1 levels indicated a U-shaped, concaved, non-linear association with all-cause mortality (P for effect = 0.011, P for non-linearity = 0.022). Dysnatraemia is an index of TIMP-1 aggravation and elevated PCWP, mean PAP; hence, it is associated with worsening all-cause mortality.Clinical Trial Registration: UMIN000023840.

Effects of Interleukin-6 on STAT3-regulated signaling in oral cancer and as a prognosticator of patient survival

ObjectivesHuman oral squamous cell carcinoma (OSCC) produces an inflammatory microenvironment enriched with cytokines including interleukin-6 (IL-6); however, the underlying molecular mechanisms of OSCC progression are unclear. We aimed to delineate the STAT3-mediated signaling pathways involved in tumor cell survival and growth. Materials and methodsImmunohistochemistry was used to semi-quantitate IL-6 and STAT3 in 111 OSCC tissues. IL-6-induced STAT3 signaling pathways and effects on tumor cell survival and progression were investigated in vitro and in xenograft mouse models. Effects of blocking IL-6-induced activation of STAT3 in an OSCC cell line were determined in vitro. ResultsA higher level of IL-6 or STAT3 in situ was associated with an unfavorable prognosis in OSCC patients with regard to both disease-free and overall survival rates. Overexpressed or exogenous IL-6 could induce SAS cell proliferationin vitroand significantly enhanced tumor growthin vivo. In addition, knockdown or inhibition of STAT3 expression in SAS cells significantly reduced tumor growth and abolished the responsiveness to IL-6 stimulation. Siltuximab or Tocilizumab could also significantly suppress IL-6-induced STAT3 phosphorylation and STAT3 nuclear translocation, resulting in a significant decrease of downstream anti-apoptotic proteins Bcl-2, Bcl-xL, and survivin. ConclusionThe IL-6 level in the tumor microenvironment could serve as a stage-independent predictor of OSCC progression and survival. Further, IL-6 may play a role in this disease through STAT3-dependent upregulation of anti-apoptotic genes and subsequent proliferation of tumor cells.

Quantification of Plasma Proteins from Idiopathic Multicentric Castleman Disease Flares and Remissions Reveals ‘Chemokine Storm’ and Separates Clinical Subtypes

Introduction: Human Herpesvirus-8(HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) is a poorly understood disease involving polyclonal lymphoproliferation, constitutional symptoms, and life-threatening multi-organ failure. Some patients experience thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO Syndrome) while others (non-TAFRO) experience thrombocytosis and hypergammaglobulinemia. Though the etiology is unknown, iMCD symptoms and disease progression are believed to be driven by a cytokine storm, often including interleukin-6 (IL-6). Anti-IL-6 therapy with siltuximab was approved by the FDA to treat iMCD based on superior efficacy compared to placebo in a randomized trial. However, approximately one-half of iMCD patients do not respond to anti-IL-6 therapy. Few rational treatment options exist for anti-IL-6 non-responders, because alternative driver cytokines and signaling pathways are not known. Furthermore, no positive diagnostic biomarkers exist for iMCD. We systematically characterized proteomic changes that occur in iMCD patients between flare and remission to identify key cytokines, signaling pathways, and cell types that may be involved in pathogenesis.Methods: Using Somalogic's modified aptamer-based proteomics platform, SOMAScan, we quantified 1,129 plasma proteins from six iMCD patients at the University of Arkansas for Medical Sciences during flare and remission. Two cases were confirmed to have TAFRO syndrome, and four cases did not have TAFRO syndrome. Proteomic data for two sets of healthy controls were obtained post-hoc and merged with the iMCD proteomic data along common calibrated proteins. Data analysis was performed using R 3.3.3.Results: Principal component analysis (PCA) revealed a distinction between iMCD samples-in flare and remission-and healthy control samples. Reactome pathway analyses identified cytokine signaling, chemokine signaling, and the complement cascade as the most enriched pathways compared to the background proteins assayed. Chemokines represented the greatest proportion of two-fold up-regulated cytokines in flare compared to interleukins and other cytokines. The chemokine, B Lymphocyte Chemoattractant (BLC)/CXCL13, was the most significantly upregulated cytokine across all patients. IL-6 was surprisingly not among the most upregulated cytokines. Five of six patients had less than two-fold up-regulation and the only patient with greater than two-fold up-regulation did not improve with anti-IL-6 receptor monotherapy. However, three of the other four patients treated with anti-IL-6 or anti-IL-6 receptor monotherapy experienced responses despite small changes in IL-6 levels between flare and remission. We observed a distinct proteomic profile between the TAFRO and non-TAFRO patients according to PCA, correlation analyses, and hierarchical clustering. The two TAFRO patients also both failed to respond to anti-IL-6 monotherapy. A large proportion of proteins significantly up- or down-regulated in non-TAFRO patients were conversely up- or down-regulated in TAFRO patients.Discussion: This study provides the first unbiased quantification of circulating proteins in iMCD patients during flare and remission. PCA of these data suggest that the proteomic profile of iMCD patients differs from that of healthy individuals even during remission. Our results support the field's assertion that iMCD involves a cytokine storm, but increased IL-6 was not uniformly present. The response of three patients to anti-IL-6 treatment suggests that IL-6 plays a critical role in these patients despite subtle changes in IL-6 levels. The increased proportion of up-regulated chemokines relative to other cytokines suggests that iMCD involves a chemokine storm. CXCL13 plays an essential role in honing B cells to germinal centers, which are uniformly dysmorphic in iMCD with either too few (atrophic) or too many B cells (hyperplastic). Lymph node stromal cells are known to produce three of the most up-regulated chemokines (CXCL13, CCL19 and CCL21), suggesting that they may play a role in pathogenesis. The distinct proteomic profiles between TAFRO (both anti-IL-6 non-responders) and non-TAFRO (responders) cases suggest that differing mechanisms may be involved. Larger studies are needed to confirm these findings and investigate chemokines in iMCD pathogenesis. DisclosuresFajgenbaum:Janssen Pharmaceuticals: Research Funding.