Increased Levels Of Interleukin-6 Research Articles

1134. Lenzilumab Treatment in COVID-19 Pneumonia Reduces Circulating Cytokines and Markers of Systemic Inflammation

Abstract Background Coronavirus disease 2019 (COVID-19) results from SARS-CoV-2-induced hyperinflammatory immune response, orchestrated by granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF increases interleukin-6 (IL-6) levels, ultimately leading to increased C-reactive protein (CRP). The LIVE-AIR trial demonstrated that lenzilumab, the GM-CSF neutralizing antibody, improved the likelihood of survival without invasive mechanical ventilation (IMV) in hospitalized COVID-19 patients requiring supplemental oxygen but not IMV. This sub-analysis correlated levels of cytokines before and after lenzilumab treatment. Methods LIVE-AIR was a phase 3, randomized, double-blind, placebo-controlled trial (NCT04351152). Patients hospitalized with COVID-19 pneumonia, requiring only supplemental oxygen, were randomized to receive lenzilumab (1800 mg in three equally divided doses of 600 mg, q8h) or placebo IV infusion, in addition to standard of care which included remdesivir and corticosteroids. Blood taken at baseline (BL) and subsequent to treatment through day 10 (D10) were obtained and analyzed by high sensitivity enzyme immunoassay for GM-CSF, IL-6, and CRP. Results Baseline IL-6 levels (Loge-transformed for all cytokines and biomarkers) were linearly correlated with higher baseline GM-CSF levels (slope=0.60, p< 0.001). Baseline CRP levels were linearly correlated with higher baseline IL-6 levels (slope=0.29, p < 0.001). GM-CSF levels decreased with lenzilumab treatment on day 1 (D1) which persisted through D10 (Table). In contrast, GM-CSF increased with placebo treatment. IL-6 levels decreased only with lenzilumab treatment. CRP following lenzilumab or placebo treatment decreased on D1 to similar levels and further decreased on D10 only with lenzilumab treatment. Cytokine Levels Associated with Lenzilumab Treatment Conclusion Lenzilumab decreased GM-CSF as well as downstream cytokines and systemic biomarkers of inflammation during the hyperinflammatory immune response of COVD-19. Disclosures Dale Chappell, MD, MBA, Humanigen, Inc: Employee|Humanigen, Inc: Ownership Interest Adrian Kilcoyne, MD, Humanigen, Inc: Employee Frank Cerasoli, PhD, Humanigen, Inc: Advisor/Consultant John Lukas, PhD, Humanigen, Inc: Advisor/Consultant Cameron Durrant, MD, Humanigen, Inc: Employee|Humanigen, Inc: Ownership Interest Zelalem Temesgen, MD, Gilead: unrestricted educational grant (to the institution)|Humanigen, Inc: Grant/Research Support|Merck: unrestricted educational grant (to the institution)|ViiV: Advisor/Consultant Christopher Polk, MD, Gilead: Advisor/Consultant Jason Baker, MD, Gilead: Grant/Research Support|Humanigen, Inc: Grant/Research Support Vincent Marconi, MD, Gilead: Grant/Research Support.

Maternal Inflammatory Biomarkers during Pregnancy and Early Life Neurodevelopment in Offspring: Results from the VDAART Study

Maternal infection and stress during the prenatal period have been associated with adverse neurodevelopmental outcomes in offspring, suggesting that biomarkers of increased inflammation in the mothers may associate with poorer developmental outcomes. In 491 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we investigated the association between maternal levels of two inflammatory biomarkers; interleukin-8 (IL-8) and C-Reactive Protein (CRP) during early (10-18 wks) and late (32-38 wks) pregnancy with offspring scores in the five domains of the Ages and Stages Questionnaire, a validated screening tool for assessing early life development. We identified a robust association between early pregnancy IL-8 levels and decreased fine-motor (β: -0.919, 95%CI: -1.425, -0.414, p = 3.9 × 10-4) and problem-solving skills at age two (β: -1.221, 95%CI: -1.904, -0.414, p = 4.9 × 10-4). Associations between IL-8 with other domains of development and those for CRP did not survive correction for multiple testing. Similarly, while there was some evidence that the detrimental effects of early pregnancy IL-8 were strongest in boys and in those who were not breastfed, these interactions were not robust to correction for multiple testing. However, further research is required to determine if other maternal inflammatory biomarkers associate with offspring neurodevelopment and work should continue to focus on the management of factors leading to increases in IL-8 levels in pregnant women.

Follow-up of Interleukin 6 and Other Blood Markers during the Hospitalization of COVID-19 Patients: A Single-Center Study

COVID-19 is a recent respiratory illness with high morbidity and mortality; therefore, the study and characterization of blood markers associated with the improvement or deterioration of COVID-19 patients are crucial. This study compared levels of interleukin 6 (IL-6), procalcitonin (PCT), D-dimer, cortisol, dehydroepiandrosterone sulfate (DHEA-S), c-reactive protein (CRP), 25-OH vitamin D, anti-SARS-CoV-2 IgG antibodies, and viremia in mild–moderate and severe–critical COVID-19 patients. In addition, the time course of blood markers was studied in severe–critical cases. The results show that levels of IL-6, PCT, D-dimer, and CRP, the cortisol/DHEA-S ratio, as well as positive viremia and anti-Spike IgGs were higher in severe–critical patients requiring hospitalization. During follow-up, most severe–critical cases displayed similar time patterns of IL-6 and viral load, whereas anti-SARS-CoV-2 antibody curves showed an inverse pattern. A decrease in IL-6 levels was associated with the improvement of COVID-19 patients, mostly through a reduced oxygen requirement. This preliminary study suggests that an increase in serum IL-6, PCT, D-dimer and CRP levels and the cortisol/DHEA-S ratio could support the selection of patients with poorer prognosis and the need for an intensive or alternative treatment. Additionally, changes in IL-6 during hospitalization were associated with changes in patient’s status mainly with a decrease in oxygen requirements, which indicates that serial measurements of IL-6 could predict the outcome of severe–critical patients with COVID-19 pneumonia.

Prognostic factors in primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal diffuse large B cell lymphoma. Despite its apparent immunopathological homogeneity, PCNSL displays a wide variability in outcome. Identifying prognostic factors is of importance for patient stratification and clinical decision-making. The purpose of this review is to focus on the clinical, neuroradiological and biological variables correlated with the prognosis at the time of diagnosis in immunocompetent patients. Age and performance status remain the most consistent clinical prognostic factors. The current literature suggests that neurocognitive dysfunction is an independent predictor of poor outcome. Cumulating data support the prognostic value of increased interleukin-10 level in the cerebrospinal fluid (CSF), in addition to its interest as a diagnostic biomarker. Advances in neuroimaging and in omics have identified several semi-quantitative radiological features (apparent diffusion restriction measures, dynamic contrast-enhanced perfusion MRI (pMRI) pattern and 18F-fluorodeoxyglucose metabolism) and molecular genetic alterations with prognostic impact in PCNSL. Validation of new biologic and neuroimaging markers in prospective studies is required before integrating future prognostic scoring systems. In the era of radiomic, large clinicoradiological and molecular databases are needed to develop multimodal artificial intelligence algorithms for the prediction of accurate outcome.

Correlation between the levels of anti-sperm antibodies and some cytokines in the seminal plasma with sperm parameters and leukocytes concentration of infertile men

Background: The aim of this work is study the relationship between sperm parameters, anti-sperm antibody and some cytokines levels for infertile men. Semen samples were studied for 88 infertile men;of these (28) infertile men with normozoospermic, (29) with oligozoospermic and (31) with asthenozoospermic ,samples were collected from Fertility Centre in Al-Sadder teaching hospital in Al-Najaf / Iraq during the period of (2/11/ 2021) and (5/2/2022). All participants underwent seminal analysis and measurement of seminal plasma antisperm antibody and some cytokine. The result of the study showed negative correlation between antisperm antibody and of interleukin (IL-1and IL-6) with sperm parameter and posative correlation with leucocytes. The presence of leucocytes in the semen is associated with an increase in levels of interleukin (IL-1and IL-6) in the seminal plasma of infertile men. The presence of antisperm antibody and interleukin (IL-1and IL-6) in the seminal plasma is associated with a negative relationship in the semen quality of infertile men.

Effect of early inflammatory reaction on ovarian reserve after laparoscopic cystectomy for ovarian endometriomas

This study aimed to investigate the effect of early inflammatory reaction on ovarian reserve of patients with ovarian endometriomas after laparoscopic cystectomy. Our retrospective case series included 112 patients with ovarian endometriomas that underwent the laparoendoscopic single-site cystectomy. Interleukin-6 (IL-6), hs-CRP, tumour necrosis factor-α (TNF-α), interleukin-17A (IL-17A) and AMH level were detected during perioperative and postoperative period. In our study, ovarian endometriomas with low AMH group were found having higher level of IL-6 than the normal AMH group in the preoperative status. On the 3rd day after operation, the change of AMH level was inversely proportional to the IL-6 level. During the follow-up within one year, it was found that the bilateral nature of the cyst and the postoperative IL-6 increased level were the risk factors for AMH not returning to baseline level. Our results suggested that inflammatory reaction is indeed involved in the damage of ovarian reserve during laparoscopic cystectomy. Hence, the negative impact of inflammatory injury should be fully considered before operation, especially young women with bilateral ovarian endometriomas. Impact Statement What is already known on this subject? Ovarian reserve in women always was reduced after the laparoscopic cystectomy. It is reported that it may be related to the use of energy instruments, haemostatic methods or the size of cysts in minimally invasive surgery. What do the results of this study add? Inflammatory reaction is indeed involved in the damage of ovarian reserve during LESS cystectomy. Interleukin-6 (IL-6) may act as the most main inflammatory factor aggravating damage of the ovarian reserve. Moreover, increased IL-6 level after surgery and bilateral cyst burden are the two risk factors for AMH not returning to baseline level within one year after surgery. What are the implications of these findings for clinical practice and/or further research? In clinic, the negative impact of inflammatory injury on ovarian reserve should be fully considered before operation, especially young women with bilateral ovarian endometriomas. Moreover, this is also the clinical basis for further study on the mechanism of inflammatory ovarian injury or the method of blocking the inflammatory response to reduce the damage of ovarian reserve after surgery.

Interleukin-6 affects the severity of olfactory disorder: a cross-sectional survey of 148 patients who recovered from Omicron infection using the Sniffin’ Sticks test in Tianjin, China

ObjectivesThe mechanism of olfactory disorder (OD) in patients with COVID-19 is unclear. Our study aimed to elucidate the relationships between inflammatory factors and OD in a sample of patients infected with the Omicron variant, with a high vaccination rate in China. MethodsThe Sniffin’ Sticks 12-item test was performed in a cross-sectional study of 148 recovered patients who were infected with the Omicron variant to evaluate OD severity. We compared demographic, laboratory, and clinical data. ResultsA total of 148 patients infected with the Omicron variant were enrolled. A total of 129 cases of OD were detected. Increased inflammation contributed to OD severity, especially in the adult group. OD was shown to be aggravated by an increase in interleukin-6 levels. The adjusted odds ratio (OR) was 2.22 (95% confidence interval 0.98-5.05, P = 0.056) after adjustment for age, sex, and vaccine characteristics. ConclusionThese findings indicated that the prevalence of OD remains high in vaccinated patients infected with the Omicron variant and that the Sniffin’ Sticks 12-item test might be a feasible method to screen for OD. Interleukin-6 may play a role in the biochemical and pathological processes underlying OD.

Effects of losartan and exercise on muscle mass and exercise endurance of old mice.

This study evaluated the effects of angiotensin II type I receptor blocker (ARB) on muscle mass and exercise capacity in healthy older animals. The effects of combined ARB and exercise training were also determined. Eighty 18-month-old mice were randomized into the control group (C), exercise group (E), losartan group (L) and losartan plus exercise group (LE). Mice in the L and LE groups received losartan from drinking water every day. Mice in the E and LE groups trained on a treadmill 30min per day, 3days per week for 4months. Exercise endurance and spontaneous physical activity of mice were measured at baseline and monthly for 4months. After 4months of intervention, serum interleukin-6 (IL-6) levels, muscle mass, and muscle fiber cross sectional area (CSA) were measured. Total antioxidant capacity (TAC), lipid peroxidation and IL-6 levels were determined in quadriceps. We found that exercise endurance only increased in the E and LE groups. Muscle TAC levels of E, L, and LE groups were greater than that in the C group. Serum IL-6 and lipid peroxidation levels were not different among groups. LE group, but not E and L groups, had greater muscle mass, larger muscle fiber CSA, and greater muscle IL-6 levels than that in the C group after 4months of intervention. These results suggest that losartan promotes the adaptions of muscle mass with exercise training in healthy older animals.

Serum concentrations of interleukin-6 and tumor necrosis factor alpha in patients with spondyloarthritis: a relationship between systemic inflammation and anemia

Aim. To assess the relationship between the activity of systemic inflammation and the hemoglobin level in patients with spondyloarthritis (SpA).Materials and methods. We examined 92 patients with SpA aged 42.9 ± 11.6 years (SpA duration – 14.8 ± 9.6 years, 55 (60%) men). We calculated the BASDAI and ASDAS-CRP scores, performed complete blood count, evaluated erythrocyte sedimentation rate (ESR), ferrokinetic parameters, C-reactive protein (CRP) level, and serum concentrations of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6).Results. Anemia was found in 52 (57%) patients: 13 (25%) patients were diagnosed with anemia of inflammation (AI), 39 (75%) individuals had a combination of AI and iron deficiency anemia. A significant increase in CRP (17.8 vs. 9.0 mg / l, respectively; p = 0.001) and ESR (23 vs. 10 mm / h, p < 0.001), a tendency toward an increase in IL-6 levels (5.4 vs. 4.1 pg / ml, p = 0.051), and no difference in TNF-α levels (3.4 vs. 3.0 pg / ml, p = 0.245) were revealed in patients with anemia compared with patients with normal hemoglobin level. The hemoglobin concentration was negatively correlated with the CRP level (r = –0.327, p = 0.001) and ESR (r = –0.527, p < 0.001). IL-6 was positively correlated with the levels of TNF-a, CRP, and ESR (r = 0.431, r = 0.361, r = 0.369; all p < 0.001). With the IL-6 concentration >10 pg / ml, the odds for anemia were 5.3 times higher (95% confidence interval: 1.4–19.9, p = 0.009).Conclusion. The relationship between the activity of systemic inflammation and anemia in patients with SpA was confirmed. Taking into account the pathogenesis of AI, the aim of antianemic treatment is to achieve remission or minimal activity of SpA. Additional studies are required to determine the effect of anti-inflammatory therapy on the development and course of anemia in patients with SpA.

Passive Sweat Based Electrochemical Sensor for Rapid Detection of IL-6

Introduction: Portable, on demand biosensing has become a key element for rapid detection of disease, particularly conditions that progress rapidly, such as infections and trauma in response to injury. Severe infections or internal traumas caused by injury can rapidly progress from the moment of onset, often before a patient has started to show symptoms, leading to progressive organ damage. In order to promptly get access to treatment, rapid testing for infection/trauma is necessary for individuals who experience a physical injury. When a person undergoes a traumatic injury, the immune system releases inflammatory cytokines, such as Interleukin-6 (IL6), in response. These cytokines induce inflammation at the site of injury as a defense mechanism against infection and further injury. The inflammatory cytokines are excreted through sweat at levels detectable by an electrochemical sensor. Using a portable, sweat-collecting electrochemical sensor, we have developed a sweat-based sensor that can detect IL6 within ultralow volumes of sweat (1-5 ul) at concentrations as low as 1 pg/ml, for rapid, noninvasive detection of infection and traumatic injury. Materials and Methods: The electrochemical sensor consists of zinc oxide electrodes on a flexible substrate. IL6 antibodies were immobilized onto the sensor surface using a thiol linker chemistry. Sensor response was measured using Electrochemical Impedance Spectroscopy (EIS) of synthetic sweat dosed with concentrations of IL6 within their physiological ranges. The spike dosing results were verified by a human study, where subjects induced IL6 elevation in their sweat. Results and Discussion: Sensor response to IL6 spike doses in synthetic sweat showed a dose dependent response to concentration of IL6, as illustrated by the Nyquist plot for sensor response to IL6 in Figure 1. These results were verified by the sensor response to pre- and post-exercise sweat of human subjects, which demonstrates an increase in IL6 levels after 10 minutes of anaerobic exercise for all subjects. This increase in IL6 post-exercise was shown to be significant for all subjects with 95% confidence using a paired T test. Conclusion: This study presents a noninvasive electrochemical sensor for rapid and early detection of infection or traumatic injury in response to a physical injury. The sensor exhibits a dose dependent response to IL6, a marker expressed at the time of injury. Sensor capability was demonstrated with human sweat pre- and post-exercise, in order to simulate the conditions following a traumatic injury, for which a significant increase in sensor response post-exercise was observed. Figure 1. Nyquist plot of Electrochemical Impedance Spectroscopy assay of IL6 in synthetic sweat. Figure 1

Apigeninidin-enriched Sorghum bicolor (L. Moench) extracts alleviate Aflatoxin B1-induced dysregulation of male rat hypothalamic-reproductive axis.

We examined the protective effect of the apigeninidin (API)-enriched fraction from Sorghum bicolor sheaths extracts (SBE-05, SBE-06, and SBE-07) against aflatoxin B1 (AFB1)-induced dysregulation of male rat's reproductive system that may trigger infertility. Male rats (160 ± 12 g) were treated with AFB1 (50 µg/kg) along with 5 or 10 mg/kg of SBE-05, SBE-06, and SBE-07 for 28 days. Subsequently, we assessed the reproductive hormone-prolactin, FSH, LH, testosterone levels, and testicular function enzymes. Moreover, we examined rats' testes, epididymis, and hypothalamus for oxidative and inflammatory stress biomarkers, caspase-9 activity and tissues pathology. We observed that comparative to AFB1 alone treated rats, API co-treatment significantly (p < 0.05) abated the AFB1-mediated decrease in prolactin and antioxidant defenses and lessened lipid peroxidation (LPO) and reactive oxygen and nitrogen species levels in the examined organs-testes, epididymis, and hypothalamus. API abated AFB1-induced hormone decreases-testosterone, FSH, and LH; and caused improvement in sperm quantity and quality. API lessened AFB1-mediated increase in pro-inflammatory cytokine, increased interleukin-10 level, an anti-inflammatory cytokine and reduced caspase-9 activities. In addition, API reduced alterations in the examined tissue histology. Our findings suggest that S. bicolor API-enrich extracts have active antioxidative, antiapoptotic, and anti-inflammatory activities, which can protect against AFB1-induced dysfunction of the hypothalamic-pituitary-gonadal axis.

NMO-IgG Induce Interleukin-6 Release via Activation of the NF-κB Signaling Pathway in Astrocytes

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) that frequently affects the optic nerve and spinal cord. Interleukin-6 (IL-6) is considered a key cytokine in the pathogenesis of NMOSD, and the level of IL-6 is significantly increased in the sera and cerebrospinal fluid (CSF) of patients with NMOSD. We have reported that the production of IL-6 depends on the JAK/STAT3 signaling pathway. However, it is not clear whether the NF-κB-dependent inflammatory response stimulated by neuromyelitis optica IgG (NMO-IgG) could also drive the production of IL-6 in astrocytes. In this study, we used an in vitro model of primary rat astrocytes stimulated by NMO-IgG to study the role of the NF-κB signaling pathway in mediating the release of IL-6. First, we confirmed that the level of IL-6 was significantly higher in the sera of NMOSD patients than that of healthy people by humoral fluid analysis and that NMO-IgG can significantly induce the release of IL-6 from astrocytes by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Then, Western blotting and immunocytochemistry showed that NMO-IgG can activate the intracellular NF-κB signaling pathway. Finally, it was found that S3633, an inhibitor of the NF-κB signaling pathway, can effectively inhibit the increase in IL-6 levels. These results prove that the production of IL-6 is partly mediated by the NF-κB signaling pathway, providing a potential effective strategy for targeted treatment of NMOSD.

Saffron extract attenuates Sofosbuvir-induced retinal neurodegeneration in albino rat.

Sofosbuvir is a novel drug candidate for the treatment of hepatitis C viral infection; however, vision loss is one of its growing adverse effects. Saffron is a natural biomolecule with a high antioxidant potential that has been efficiently used in some diseases caused by oxidative stress. This study evaluated Sofosbuvir's neurodegenerative effect on the retina of albino rat and examined the potential protective role of saffron aqueous extract. Twenty-one adult male albino rats were randomly divided into three groups: Control, Sofosbuvir-treated (41.1 mg/kg /day for 6 weeks), and Sofosbuvir + Saffron co-treated groups. Retinal specimens were biochemically analyzed for malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, light and transmission electron microscopic examination, as well as immunohistochemical staining for Caspase-3, COX-2, and GFAP were performed. Sofosbuvir treatment caused a significant increase in retinal MDA, IL-6, and TNF-α levels coupling with a significant decrease in retinal total antioxidant capacity level. Histopathological findings revealed disturbed retinal architecture, detached pigment epithelium, vacuolated photoreceptors, in addition to a significant decrease in the thicknesses of both outer and inner nuclear layers, and the number of ganglionic cells. Ultrastructural examination revealed extensive degenerative changes in all retinal layers. Caspase-3, COX-2, and GFAP immunohistochemical expressions were significantly increased. Meanwhile, concomitant treatment with Saffron significantly improved retinal redox status, inflammation, histological, and ultrastructural parameters. Saffron may protect the retina from the hazardous effects of Sofosbuvir. Saffron could be used as an adjuvant therapy to protect patients receiving Sofosbuvir from retinal damage.

Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway.

M1 microglia induce neuroinflammation-related neuronal death in animal models of spontaneous subarachnoid haemorrhage. Zileuton is a 5-lipoxygenase inhibitor that reduces the levels of downstream pro-inflammatory cytokines. This study aimed to investigate whether zileuton inhibits microglial activation and describe its underlying mechanisms. BV-2 cells were exposed to 1 mg/mL haemolysate for 30 min, followed by treatment with different concentrations (5, 10, 15, or 20 μM) of zileuton for 24 h. The cells were then assessed for viability, polarisation, and protein expression levels. Haemolysate increases the viability of BV-2 cells and induces M1 polarisation. Subsequent exposure to high concentrations of zileuton decreased the viability of BV-2 cells, shifted the polarisation to the M2 phenotype, suppressed the expression of 5-lipoxygenase, decreased tumour necrosis factor α levels, and increased interleukin-10 levels. Furthermore, high concentrations of zileuton suppressed the expression of myeloid differentiation primary response protein 88 and reduced the phosphorylated-nuclear factor-kappa B (NF-kB)/NF-kB ratio. Therefore, phenotype reversal from M1 to M2 is a possible mechanism by which zileuton attenuates haemolysate-induced neuroinflammation after spontaneous subarachnoid haemorrhage.

Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis.

We describe the study of a novel aptamer-based candidate for treatment of seropositive rheumatoid arthritis. The candidate is a nanoparticle-formulated cyclic citrullinated peptide aptamer, which targets autoantibodies and/or the immune reactions leading to antibody production. Due to its specificity, the peptide aptamer nanoparticles might not interfere with normal immune functions as seen with other disease-modifying antirheumatic drugs. Over a 3-week course of treatment, joint swelling and arthritis score in collagen-induced rats were significantly decreased compared with animals treated with phosphate-buffered saline, unloaded nanoparticles, or nanoparticles with a noncitrullinated control peptide. The reduction in joint swelling was associated with decreased anticitrullinated peptide autoantibody levels in the blood. Treatment with aptamer nanoparticles also increased interleukin-10 levels. The effect seen with the proposed treatment candidate could be mediated by upregulation of anti-inflammatory mediators and decreased levels of anticitrullinated peptide antibodies.

Increased interleukin-6 levels associated with malaria infection and disease severity: a systematic review and meta-analysis

Interleukin-6 (IL-6) is generated by immune cells during infection with malaria parasites and they are associated with the immunopathogenesis of malaria. The present systematic review and meta-analysis aimed to compare the differences in IL-6 levels between several groups of patients with malaria and healthy control groups. The systematic review was registered at PROSPERO with a registration number: CRD42021290753. Systematic literature searches were conducted in PubMed, Web of Science, and Scopus until November 7, 2021 to obtain studies that documented IL-6 levels in patients with malaria. The quality of the included studies was assessed using critical appraisal tools from the Joanna Briggs Institute. Differences in the mean IL-6 levels among patients with: (1) severe and non-severe malaria, (2) uncomplicated malaria and controls, (3) uncomplicated and asymptomatic malaria, (4) asymptomatic malaria and healthy controls, and (5) those that died or survived were estimated using a random-effects model. Forty-three of 1,969 studies were included in the systematic review. Results of the meta-analysis showed that patients with severe malaria had higher mean IL-6 levels than those with non-severe malaria [P = 0.04, weight mean difference (WMD) = 96.63 pg/mL, 95% confidence interval (CI) = 0.88 − 19.38 pg/mL, I2 = 99.9%, 13 studies]. Patients with uncomplicated malaria had higher mean IL-6 levels than the controls (P < 0.001, WMD = 42.86 pg/mL, 95% CI = 30.17 − 55.56 pg/mL, I2 = 100%, 17 studies). No differences in the mean levels of IL-6 were found between patients with uncomplicated malaria and those with asymptomatic malaria (P = 0.063, WMD = 42.07 pg/mL, 95% CI = − 2.23 pg/mL to − 86.37 pg/mL, I2 = 99.1%, 8 studies), or between patients with asymptomatic malaria and healthy controls (P = 0.45, WMD = 1.67 pg/mL, 95% CI = − 2.73 pg/mL to − 6.07 pg/mL, I2 = 98.1%, 2 studies). A higher mean level of IL-6 was observed in patients who died compared with the levels of those who survived (P = 0.007, WMD = 1,399.19 pg/mL, 95% CI = 384.16 − 2,414.2 pg/mL, I2 = 93.1%, 4 studies). Our meta-analysis of the pooled evidence can be used to guide future studies in which IL-6 levels are measured during malaria outbreaks to monitor malaria severity. Heterogeneity of the effect estimate among the included studies was the main limitation of this analysis. In conclusion, significantly increased levels of IL-6 were observed in patients with severe malaria compared with those in patients with non-severe malaria, which indicates that IL-6 is a candidate marker for severe malaria. Future studies should investigate the sensitivity and specificity of increased IL-6 levels to determine the effectiveness of assessments of IL-6 levels monitoring of malaria infection and severity.

Correlation of Interleukin-6 Levels with Clinical Features and Chest X-Ray Imaging in Coronavirus Disease-19 (COVID-19) Patients at Dr. Mohammad Hoesin General Hospital Palembang

Background. COVID-19 infection, both moderate and severe symptoms can cause pneumonia that can be detected on a chest X-ray. Along with the increasing severity of the clinical picture of COVID 19, it can also trigger a cytokine storm, one of which is an increase in Interleukin-6 levels. This study was conducted to see the correlation between IL-6 levels with clinical features and chest radiographs in patients with COVID-19&#x0D; Methods. This research is a cross-sectional study using an observational analytic. The samples in this study were confirmed COVID-19 patients who were being treated at Dr. Mohammad Hoesin General Hospital, Palembang. A history and physical examination were performed to determine the clinical picture as well as a chest X-ray and IL-6 levels.&#x0D; Results. There were 31 samples of COVID 19 patients. High levels of IL-6 were found in 26 (83.9%) samples. The clinical picture of the patient was dominated by dyspnea as much as 19 (61.3%), fever 16 (5.6%), low O2 saturation 12 (38.4%) and a chest X-ray of pneumonia 26 (83.9%). There was a significant relationship (P&lt;0.05) between IL-6 levels with clinical features and chest X-rays. The R-value on the thorax with pneumonia (0.692), lesion area (0.711) and clinical features with temperature (0.906), respiratory rate (0.706) indicated a strong correlation, while O2 (-0.732) indicated a strong negative correlation.&#x0D; Conclusion. There is a significantly strong correlation between Interleukin 6 levels with clinical features and chest X-rays in patients with COVID-19.

Cytotoxic and pro-inflammatory effects of molybdenum and tungsten disulphide on human bronchial cells

Abstract This study aimed to investigate the cytotoxicity and pro-inflammatory responses induced by tungsten disulphide (WS2) and molybdenum disulphide (MoS2) nanoparticles (NPs) in human bronchial cells (BEAS-2B). For cytotoxicity assessment, the cells were exposed to different concentrations (2.5–200 µg/mL) of WS2-NPs or MoS2-NPs for 24 and 48 h and then the MTT assay was performed. Afterwards, long-term toxicity was assessed by the colony forming efficiency assay (CFEA) during a 10 days’ exposure of the cells. For pro-inflammatory responses, the expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β) mRNA was estimated by the real-time PCR method. Both nanomaterials showed similar cytotoxic effects on BEAS-2B cells assessed by the MTT assay, i.e. reduction in cell viability to approx. 60–70% at concentrations of 2.5 and 5 μg/mL after 24 and 48 h. The percentage viability remained relatively constant at this level across all concentrations above 5 μg/mL. In long-term exposure, both nanomaterials inhibited colony formation in a wide range of concentrations up to 100 µg/mL. MoS2-NPs were slightly more cytotoxic than WS2-NPs. Additionally, MoS2-NPs caused an increase in mRNA levels of cytokines, IL-1β, and IL-6 at concentration of 50 µg/mL, while WS2-NPs did not cause any changes in the level of mRNA for both cytokines. We also visualised the changes in the cells as a result of WS2-NPs or MoS2-NPs exposure (2.5 and 25 µg/mL) via holotomographic microscopy. This work demonstrates the hazardous potential of both nanomaterials and indicate that WS2 and MoS2 nanoparticles should be included in the occupational risk assessment.

Baicalin inhibits LPS/IFN-γ-induced inflammation via TREM2/TLR4/NF-κB pathway in BV2 cells

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 μmol·L~(-1)) baicalin group, medium-dose(10 μmol·L~(-1)) baicalin group, high-dose(20 μmol·L~(-1)) baicalin group, and minocycline(10 μmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1β(IL-1β), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1β, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1β, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P&lt;0.01), rise of the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P&lt;0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1β, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P&lt;0.01), reduction in the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P&lt;0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.

Ibrutinib reverses IL-6-induced osimertinib resistance through inhibition of Laminin \u03b15/FAK signaling

Osimertinib, a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the first-line standard-of-care for EGFR-mutant non-small cell lung cancer (NSCLC) patients, while acquired drug resistance will inevitably occur. Interleukin-6 (IL-6) is a keystone cytokine in inflammation and cancer, while its role in osimertinib efficacy was unknown. Here we show that clinically, plasma IL-6 level predicts osimertinib efficacy in EGFR mutant NSCLC patients. Highly increased IL-6 levels are found in patients with acquired resistance to osimertinib. Addition of IL-6 or exogenous overexpression of IL-6 directly induces osimertinib resistance. Proteomics reveals LAMA5 (Laminin α5) and PTK2, protein tyrosine kinase 2, also called focal adhesion kinase (FAK), are activated in osimertinib-resistant cells, and siRNA knockdown of LAMA5 or PTK2 reverses IL-6-mediated osimertinib resistance. Next, using a large-scale compound screening, we identify ibrutinib as a potent inhibitor of IL-6 and Laminin α5/FAK signaling, which shows synergy with osimertinib in osimertinib-resistant cells with high IL-6 levels, but not in those with low IL-6 levels. In vivo, this combination inhibits tumor growth of xenografts bearing osimertinib-resistant tumors. Taken together, we conclude that Laminin α5/FAK signaling is responsible for IL-6-induced osimertinib resistance, which could be reversed by combination of ibrutinib and osimertinib.