Lower Levels Of IL-6 Research Articles

Nasal biomarkers of immune function differ based on smoking and respiratory disease status.

Respiratory biomarkers have the potential to identify airway injury by revealing inflammatory processes within the respiratory tract. Currently, there are no respiratory biomarkers suitable for clinical use to identify patients that warrant further diagnostic work-up, counseling, and treatment for toxic inhalant exposures or chronic airway disease. Using a novel, noninvasive method of sampling the nasal epithelial lining fluid, we aimed to investigate if nasal biomarker patterns could distinguish healthy nonsmoking adults from active smokers and those with chronic upper and lower airway disease in this exploratory study. We compared 28 immune mediators from healthy nonsmoking adults (n=32), former smokers with COPD (n=22), chronic rhinosinusitis (CRS) (n=22), and smoking adults without airway disease (n=13). Using ANOVA, multinomial logistic regressions, and weighted gene co-expression network analysis (WGCNA), we determined associations between immune mediators and each cohort. Six mediators (IL-7, IL-10, IL-13, IL-12p70, IL-15, and MCP-1) were lower among disease groups compared to healthy controls. Participants with lower levels of IL-10, IL-12p70, IL-13, and MCP-1 in the nasal fluid had a higher odds of being in the COPD or CRS group. The cluster analysis identified groups of mediators that correlated with disease status. Specifically, the cluster of IL-10, IL-12p70, and IL-13, was positively correlated with healthy and negatively correlated with COPD groups, and two clusters were correlated with active smoking. In this exploratory study, we preliminarily identified groups of nasal mucosal mediators that differed by airway disease and smoking status. Future prospective, age-matched studies that control for medication use are needed to validate these patterns and determine if nasosorption has diagnostic utility for upper and lower airway disease or injury.

Correlation of high serum interleukin-6 with clinical outcome and T cell response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

596 Background: We elucidated the clinical and immunologic implications of serum interleukin (IL)-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev). Methods: We prospectively enrolled 165 patients with unresectable HCC (Discovery cohort: 84 patients from three centers; Validation cohort: 81 patients from one center). Baseline blood samples were analyzed using a flow cytometric bead array. The tumor immune microenvironment was analyzed using RNA sequencing. Results: In the Discovery cohort, clinical benefit (CB) was defined as a complete or partial response or stable disease for ≥ 6 months. Among various blood-based biomarkers, the serum IL-6 level was significantly higher in patients without CB than in those with CB (mean 11.56 vs. 5.05 pg/mL, P=0.02). The optimal cutoff value for high IL-6 was determined as 18.49 pg/mL using maximally selected rank statistics, and 15.2% of patients were identified to have high IL-6 levels at baseline. In both the Discovery and Validation cohorts, patients with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev compared with that of patients with low IL-6 levels. In the multivariable Cox regression analysis, the clinical implication of high IL-6 levels persisted even after adjustment for various confounding factors. Patients with high IL-6 levels showed reduced interferon-γ and tumor necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and CD8+ T-cell proliferation. Finally, patients with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumor microenvironment. Conclusions: High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment.

Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection.

The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates pathogen-induced immune responses via activation of the MyD88-dependent TLR signaling pathway. In the current study, the frequencies of IRF5+ DCs and the association with innate cytokine responses in SARS-CoV-2 infected individuals with different disease courses were investigated. In addition to a decreased number of mDC and pDC subsets, we could show reduced relative IRF5+ frequencies in mDCs of SARS-CoV-2 infected individuals compared with healthy donors. Functionally, mDCs of COVID-19 patients produced lower levels of IL-6 in response to in vitro TLR7 stimulation. IRF5+ mDCs more frequently produced IL-6 and TNF-α compared to their IRF5- counterparts upon TLR7 ligation. The correlation of IRF5+ mDCs with the frequencies of IL-6 and TNF-α producing mDCs were indicators for a role of IRF5 in the regulation of cytokine responses in mDCs. In conclusion, our data provide further insights into the underlying mechanisms of TLR7-dependent immune dysfunction and identify IRF5 as a potential immunomodulatory target in SARS-CoV-2 infection.

Immunomodulatory effects of bone marrow-derived Mesenchymal stem cells on BALB/c mice model with induced Systemic lupus erythematosus (SLE).

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease that causes acute inflammation in most body tissues. The current study aims to determine levels of some cytokines and chemokines in BALB/c mice with SLE and treatment by using BALB/c Mesenchymal stem cells (BM-MSCs). Forty BALB/c male mice were divided into four groups equally. The first and second groups received activated lymphocyte-derived DNA (ALD DNA) for induction of SLE. The second group received BM-MSCs/IV after the appearance of SLE clinical signs. The third group received BM-MSCs only, while the fourth group (control group) received PBS. All the study groups examine levels of IL-10, IL-6, TGFβ1, VEGF, CCL-2, CCL-5/RANTES, IFNγ, and ICAM -1 by ELISA kits. The cytokines levels are determined in all the study groups. There was a significant increase in ANA and anti-dsDNA levels in the first group, while there was a decrease in the second group (treatment by BM-MSCs). There is no significant difference between the third and control groups in ANA and anti-dsDNA levels. The first group showed a significant increase in IL-6, CCL-5/RANTES, VEGF, ICAM, CCL-2, and IFNγ levels and a decrease in IL-10 and TGFβ1. The second group showed low levels of IL-6, CCL-5/RANTES, VEGF, ICAM, CCL-2/MCP-1, and IFNγ but a high level of IL-10 and TGFβ1 as compared with the control group. The third group has no significant differences from the control group in all the tested parameters. BM-MSCs have an essential therapeutic role in the functional regulation of cytokines and chemokines in mice with SLE.

P033 The assessment of serum cytokines at baseline could predict mucosal healing in patients with Crohn’s disease treated with ustekinumab. A prospective study.

Abstract Background Ustekinumab (UST) is a monoclonal IgG1 antibody binding the p40 subunit of IL-12 and IL-23. The blockage of the activation of the heterodimer IL-12/IL-23 inhibits the differentiation of Th1 and Th17 cells, reducing the inflammatory cascade typical of Crohn’s disease (CD). Some patients with CD achieve mucosal healing after one year of UST therapy, whereas others experience primary non-response or loss of response. No biomarkers are currently available to predict therapeutic response to UST. The aim of this prospective study was to identify one or more biomarkers able to predict mucosal healing in patients with CD treated with UST. Methods We prospectively enrolled all consecutive CD patients treated with UST, following the current guidelines. A blood sample was drawn before UST infusion at week 0 (baseline), 24 and 48, and serum cytokines IL1α, IL-1β, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-22, IL-23 and IL-33 were evaluated by a fluorescence assay. At the same timepoints, Fecal Calprotectin (FC) was assessed. A colonoscopy was performed before starting the treatment and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing, defined as a Simple Endoscopic Score for CD <2. Results Out of 44 patients enrolled, 22 (50%) achieve mucosal healing at the end of follow up. Baseline IL-23 levels were higher in responders than in non-responders (Mann-Whitney test, p-value<0.001), whereas higher baseline levels of IL-1α are associated with non-response (p=0.03). We also observed a higher probability of mucosal healing in those with lower levels of IL-6 at baseline (p=0.05). A borderline statistically significant association was observed for baseline FC, which values were lower in responders than in non-responders (Mann-Whitney test, p=0.098). No significant differences were observed with regard to the baseline levels of the other cytokines. FC levels decreased over time in responders, whereas its values did not change over time in non-responders (test for the interaction between time and outcome, p<0.001). IL-13 presented a homogenously decreasing time trend regardless the outcomes (test for the association with time and outcome, p=0.019). No significant time trend was observed with regard to the other cytokines. Conclusion Baseline serum levels of IL-23, IL-1α and IL-6, as well as the decrease of FC over time, showed a good reliability in predicting therapeutic outcome to UST in CD in terms of mucosal healing. These biomarkers could help clinicians in the perspective of a better management of UST therapy, identifying early the patients with higher probability to respond to the treatment.

Reproducibility of the new Leishmania vaccine: Changes in T1, T2 and spleen white pulp responses after re- exposure to live promastigote of Leishmania major

Introduction: Human leishmaniasis is distributed worldwide and is mainly in the tropics and subtropics, with a prevalence of 12 million cases and an approximately incidence of 0.5 million cases of VL and 1.5 million cases of cutaneous leishmaniasis (CL). Leishmania parasites are vector-born protozoan pathogens found in tropical and subtropical regions of both the old and new world. The disease in human can be divided into cutaneous, visceral, and mucosal syndromes. The aim of this study was more experiments over our previous new formulation leishmania major vaccine which had satisfactory experiments results. Method: For detail procedure refers to author’s previous publications. Briefly, hundred and twenty Balb/cmice were randomly divided into four groups as LT, LB, LBT and control groups. LT, LB and LBT injected subcutaneously with the antigen and the same booster doses with two weeks intervals. The expansion rates of the spleen white pulp size was evaluated using a light microscope and the levels of the serum Th1 (IFN- γ, IL-12) and Th2 (IL-4, IL-10) cytokines measured with the ELISA method. Results: Comparing to the LT and LB groups, the LBT group had highest levels of serum IL12, lowest levels of IL10 and highest increase in the spleen white pulp size. Significant correlation was observed between IL12 and IL10 but not IFN gamma or IL4. Conclusion: present study indicated that the LBT group which received crude cocktail leishmania antigen plus alcoholic extract of Teucrium polium and BCG as adjuvant showed satisfactory cytokines profile comparing to groups LT and LB,since highest levels of IL12 and lower levels of IL10 which could help the infected subjects to inhibit or eradication the intracellular leishmania amastigotes, and also was seen highest increase in the spleen white-pulp size which pointed to the synergistic effects of alcoholic extract of T. polium and BCG.

Lower Creatine Kinase, IL-6 Levels and Femoral Offset Values Lead to Better Outcome Harris Hip Score Post Bipolar Hemiarthroplasty Surgery Day 14 and Day 30

Bipolar Hemiarthroplasty (HA) procedure allows patients after a neck femur fracture to be able to perform early mobilization. Hence complications due to prolonged bed rest could be prevented. Early mobilization should be achieved immediately after bipolar HA surgery. There are several factors affecting early mobilization in patients, some of which include tissue damage during surgery (creatine kinase), inflammatory status of patients (IL-6) and implant position (femoral offset). This study aims to show whether lower levels of creatine kinase, IL-6 and femoral offset can result in better Harris Hip Score following Bipolar HA surgery day 14 and day 30. By knowing the influencing factors, it is hoped that more accurate management could be carried out. Thus, the outcome parameters of early mobilization in the form of returning to daily life and work activities are getting better and the risk of complications can be avoided. This study compared the Harris Hip Score (HHS) in patients who'd already had Bipolar Hemiarthroplasty using a prospective cohort study design (Bipolar HA) who met the inclusion criteria at the Central General Hospital (RSUP) Prof I.G.N.G Ngoerah Denpasar and provided them informed consent. In order to do descriptive analysis, normality and homogeneity tests, and proportion comparison analysis, the research data was entered into a research sheet and processed using a computer and the SPSS for Windows version 26 program. In this study, the sample data (n=32) was not normally distributed. Lower levels of IL-6 (< 15 pg/ml), and FO values ​​(​​< 42.5 mm) resulted in better HHS values ​​in patients following Bipolar HA surgery day-14. Additionally, lower levels of CK (< 75 U/L), IL-6 (< 15 pg/ml), and FO values (​​< 42.5 mm) ​​resulted in better HHS values ​​in patients following bipolar HA surgery on day-30. Chi-Square analysis showed that the results of CK levels day-14 were statistically insignificant (p= 0.072>0.05), while the results of CK levels day-30 were statistically significant (p=0.033<0.05). Moreover, chi-Square analysis showed that the results of day-14 and day-30 were statistically significant on IL-6 levels (p-0.016<0.05 and p= 0.015<0.05), and FO values (p= 0.012<0.05 and p-0.033<0.05). It is concluded that lower levels of IL-6, and FO values resulted in better HHS values in patients following Bipolar HA surgery day-14. Additionally, lower levels of CK, IL-6, and FO values resulted in better HHS values in patients following bipolar HA surgery on day-30.

Enhanced Solubility and Biological Activity of Dexibuprofen-Loaded Silica-Based Ternary Solid Dispersions.

The current study was designed to formulate ternary solid dispersions (TSDs) of dexibuprofen (Dex) by solvent evaporation to augment the solubility and dissolution profile, in turn providing gastric protection and effective anti-inflammatory activity. Initially, nine formulations (S1 to S9) of binary solid dispersions (BSDs) were developed. Formulation S1 comprising a 1:1 weight ratio of Dex and Syloid 244FP® was chosen as the optimum BSD formulation due to its better solubility profile. Afterward, 20 TSD formulations were developed using the optimum BSD. The formulation containing Syloid 244FP® with 40% Gelucire 48/16® (S18) and Poloxamer 188® (S23) successfully enhanced the solubility by 28.23 and 38.02 times, respectively, in pH 6.8, while dissolution was increased by 1.99- and 2.01-fold during the first 5 min as compared to pure drug. The in vivo gastroprotective study in rats suggested that the average gastric lesion index was in the order of pure Dex (8.33 ± 2.02) > S1 (7 ± 1.32) > S18 (2.17 ± 1.61) > S23 (1.83 ± 1.04) > control (0). The in vivo anti-inflammatory study in rats revealed that the percentage inhibition of swelling was in the order of S23 (71.47 ± 2.16) > S18 (64.8 ± 3.79) > S1 (54.14 ± 6.78) > pure drug (18.43 ± 2.21) > control (1.18 ± 0.64) after 6 h. ELISA results further confirmed the anti-inflammatory potential of the developed formulation, where low levels of IL-6 and TNF alpha were reported for animals treated with S23. Therefore, S23 could be considered an effective formulation that not only enhanced the solubility and bioavailability but also reduced the gastric irritation of Dex.

Post-vaccination serum cytokines levels correlate with breakthrough influenza infections

Post-vaccination cytokine levels from 256 young adults who subsequently suffered breakthrough influenza infections were compared with matched controls. Modulation within the immune system is important for eliciting a protective response, and the optimal response differs according to vaccine formulation and delivery. For both inactivated influenza vaccine (IIV) and live attenuated influenza vaccines (LAIV) lower levels of IL-8 were observed in post-vaccination sera. Post-vaccination antibody levels were higher and IFN-γ levels were lower in IIV sera compared to LAIV sera. Subjects who suffered breakthrough infections after IIV vaccination had higher levels of sCD25 compared to the control group. There were differences in LAIV post-vaccination interleukin levels for subjects who subsequently suffered breakthrough infections, but these differences were masked in subjects who received concomitant vaccines. Wide variances, sex-based differences and confounders such as concomitant vaccines thwart the establishment of specific cytokine responses as a correlate of protection, but our results provide real world evidence that the status of the immune system following vaccination is important for successful vaccination and subsequent protection against disease.

High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma

We elucidated the clinical and immunologic implications of serum IL-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev). We prospectively enrolled 165 patients with unresectable HCC (discovery cohort: 84 patients from three centres; validation cohort: 81 patients from one centre). Baseline blood samples were analysed using a flow cytometric bead array. The tumour immune microenvironment was analysed using RNA sequencing. In the discovery cohort, clinical benefit 6 months (CB6m) was defined as complete or partial response, or stable disease for ≥6 months. Among various blood-based biomarkers, serum IL-6 levels were significantly higher in participants without CB6m than in those with CB6m (mean 11.56 vs. 5.05pg/ml, p= 0.02). Using maximally selected rank statistics, the optimal cut-off value for high IL-6 was determined as 18.49pg/ml, and 15.2% of participants were found to have high IL-6 levels at baseline. In both the discovery and validation cohorts, participants with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev treatment compared with those with low baseline IL-6 levels. In multivariable Cox regression analysis, the clinical implications of high IL-6 levels persisted, even after adjusting for various confounding factors. Participants with high IL-6 levels showed reduced interferon-γ and tumour necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and proliferation of CD8+ T cells. Finally, participants with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumour microenvironment. High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment. Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Effect of Familial Longevity on Frailty and Sarcopenia: A Case-Control Study.

Familial longevity confers advantages in terms of health, functionality, and longevity. We sought to assess potential differences in frailty and sarcopenia in older adults according to a parental history of extraordinary longevity. A total of 176 community-dwelling subjects aged 65-80 years were recruited in this observational case-control study, pair-matched 1:1 for gender, age, and place of birth and residence: 88 centenarians' offspring (case group) and 88 non-centenarians' offspring (control group). The main variables were frailty and sarcopenia based on Fried's phenotype and the European Working Group on Sarcopenia in Older People (EWGSOP) definitions, respectively. Sociodemographics, comorbidities, clinical and functional variables, the presence of geriatric syndromes, and laboratory parameters were also collected. Related sample tests were applied, and conditional logistic regression was performed. Cases had a higher percentage of robust patients (31.8% vs. 15.9%), lower percentages of frailty (9.1% vs. 21.6%) and pre-frailty (59.1% vs. 62.5%) (p = 0.001), and lower levels of IL-6 (p = 0.044) than controls. The robust adjusted OR for cases was 3.00 (95% CI = 1.06-8.47, p = 0.038). No significant differences in muscle mass were found. Familial longevity was also associated with less obesity, insomnia, pain, and polypharmacy and a higher education level and total and low-density lipoprotein cholesterol. The results suggest an inherited genetic component in the frailty phenotype, while the sarcopenia association with familial longevity remains challenging.

Irisin prevents hypoxic-ischemic brain damage in rats by inhibiting oxidative stress and protecting the blood-brain barrier

Hypoxic-ischemic encephalopathy (HIE) is associated with excessive inflammation, blood-brain barrier dysfunction, and oxidative stress. Irisin can reduce inflammation and ameliorate oxidative stress; however, its effects on hypoxic-ischemic brain damage in newborns are unknown. Newborn Sprague-Dawley rats were subjected to hypoxic-ischemic injury and irisin treatment. TUNEL staining assays, the albumin-Evans blue dye extravasation method, an antioxidants detection kit, quantitative reverse-transcriptase PCR, enzyme linked immunosorbent assay, Western blot analysis, immunohistochemistry, and electron microscopy were used to investigate the possible mechanisms underlying the prevention of HIE by irisin. We discovered that rats affected by HIE and administered irisin had lower levels of IL-6 (but not TNF-α or IL-1β) less oxidative stress, and enhanced blood-brain barrier integrity. Irisin can effectively attenuate brain damage by reducing oxidative stress and protecting the blood-brain barrier.

Immunoprotective effect of recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice

To evaluate the immunoprotective effect of active immunization with recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice. Female BALB/c mice at 6 weeks of age, each weighing approximately 20 g, were divided into the recombinant protein immunization group, the infection control group and the normal control group, of 25, 18, 15 mice in each group, respectively. Mice in the recombinant protein immunization group were given active immunization with recombinant BmPPIase protein, and 18 mice with the highest antibody titers were intraperitoneally injected with 100 μL of B. microti-infected whole blood 2 weeks after the last immunization. Mice in the infection control group were intraperitoneally injected with 100 μL of B. microti-infected whole blood, while 15 mice in the normal control group received no treatment. Blood samples were collected from mice in the recombinant protein immunization group and the infection control group on days 0 to 30 post-immunization for detection of B. microti infection, and blood samples were collected on days 0, 7, 14, 21, and 28 post-immunization for routine blood tests with a blood cell analyzer and for detection of serum cytokines using cytometric bead array. Anti-BmPPIase antibodies were detected in 25 mice in the recombinant protein immunization group 2 weeks after the last immunization, with titers of 5 × 103 to 8 × 104. B. microti infection rate peaked in mice in both the recombinant protein immunization and the infection control group on day 7 post-immunization, with positive infection rates of 13.3% and 50.0%, and there were significant differences between the two groups in terms of B. microti infection rate on days 3 (χ2= 113.18, P < 0.01), 5 (χ2 = 475.22, P < 0.01), 7 (χ2 = 465.98, P < 0.01) and 9 post-infection (χ2= 18.71, P < 0.01), while the B. microti infection rate tended to be 0 in both groups on day 11 post-immunization. Routine blood tests showed higher red blood cell counts [(5.30 ± 0.50) × 1012 to (9.87 ± 0.24) × 1012 counts/L)] and hemoglobin levels [(89.67 ± 22.80) to (148.60 ± 3.05) g/L)] in the recombinant protein immunization group than in the infection control group on days 0 to 28 post-immunization. Cytometric bead array detected higher serum interferon-γ [(748.59 ± 17.56) to (3 858.28 ± 1 049.10) fg/mL], tumor necrosis factor-α [(6 687.34 ± 1 016.64) to (12 708.13 ± 1 629.79) fg/mL], interleukin (IL)-6 [(611.05 ± 75.60) to (6 852.68 ± 1 554.00) fg/mL] and IL-17a [(167.68 ± 185.00) to (10 849.27 ± 355.40) fg/mL] and lower IL-10 levels [(247.65 ± 138.00) to (18 787.20 ± 2 830.22) fg/mL] in the recombinant protein immunization group than in the infection control group during the study period. Recombinant BmPPIase protein induces up-regulation of interferon-γ, tumor necrosis factor-α and presents a high immunoprotective activity against B. microti infection in mice, which is a potential vaccine candidate protein.

Age-related Differences in Immune Reactions to SARS-CoV-2 Spike and Nucleocapsid Antigens.

The manifestation and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections show a clear correlation to the age of a patient. The younger a person, the less likely the infection results in significant illness. To explore the immunological characteristics behind this phenomenon, we studied the course of SARS-CoV-2 infections in 11 households, including 8 children and 6 infants/neonates of women who got infected with SARS-CoV-2 during pregnancy. We investigated the immune responses of peripheral blood mononuclear cells (PBMCs), umbilical cord blood mononuclear cells (UCBCs), and T cells against spike and nucleocapsid antigens of SARS-COV-2 by flow cytometry and cytokine secretion assays. Upon peptide stimulation, UCBC from neonates showed a strongly reduced IFN-γ production, as well as lower levels of IL-5, IL-13, and TNF-α alongside with decreased frequencies of surface CD137/PD-1 co-expressing CD4+ and CD+8 T cells compared with adult PBMCs. The PBMC response of older children instead was characterized by elevated frequencies of IFN-γ+ CD4+ T cells, but significantly lower levels of multiple cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, and TNF-α) and a marked shift of the CD4+/CD8+ T-cell ratio towards CD8+ T cells in comparison to adults. The increased severity of SARS-CoV-2 infections in adults could result from the strong cytokine production and lower potential to immunomodulate the excessive inflammation, while the limited IFN-γ production of responding T cells in infants/neonates and the additional higher frequencies of CD8+ T cells in older children may provide advantages during the course of a SARS-CoV-2 infection.

Patterns of cytokine and chemokine expression in peripheral blood of patients with COVID-19 associated with disease severity.

Cytokine dysregulation has been proposed as one of the main culprits for severe COVID-19 and poor prognosis. We examined the parallel presence of lymphopoietic, proinflammatory, Th1, Th2, regulatory cytokines, and chemokines in the serum of 47 patients with mild, moderate, and severe COVID-19 and evaluated the association between cytokine concentrations and disease severity. A multiplex quantitative cytokine analysis ProcartaPlex™ immunoassay was applied, using the LuminexTM 200X detection system (Invitrogen). The concentrations of twelve cytokines: IL-18, IFN-gamma, TNF-alpha; IL-21; IL-1alpha, IL-1beta, IL-6, IL-22; IL-10, IL-1RA; IL-7 and IFN-alpha were consistently elevated in the studied serum samples. All examined chemokines-Eotaxin, GRO-alpha, IL-8, IP-10, MCP-1, MIP-1alpha, MIP-1beta, SDF-1alpha, and RANTES, were detectable in all studied groups, confirming their importance in mediating the adaptive immune response regardless of disease severity. The serum concentrations of six mediators: IL-1beta, IL-6, IL-18, IL-10, IL-8, and IP-10, showed statistically significant differences among the groups with different disease severity. IL-6, IL-1beta, and IL-10 were more significantly elevated in severe cases while milder symptoms were associated with lower levels of IL-8 and IP-10. Overall, the studied chemokines demonstrated an associated production in acute COVID-19 infection. A strong correlation was observed between the Th1 mediators IL-18 and IL-10 and the proinflammatory IL-6 in the severe COVID-19 group. Our results indicated that severe COVID-19 was characterized by a dysregulated cytokine pattern whereby the Th1 immune response is outweighed by the immunoregulatory response, while inhibitory signals cannot balance the hyperinflammatory response.

Chronic Oral Administration of Aluminum Hydroxide Stimulates Systemic Inflammation and Redox Imbalance in BALB/c Mice.

The present study is aimed at investigating the long-term effects of the aluminum hydroxide administration in the small intestine, lung, liver, and kidney of male BALB/c mice. The mice received via orogastric gavage phosphate buffered or 10 mg/kg aluminum hydroxide 3 times a week for 6 months. Administration of aluminum hydroxide decreased hemoglobin, hematocrit, and erythrocyte. In the blood, kidney and liver function markers were evaluated, and long-term administration of aluminum hydroxide led to an increase in AST levels and a decrease in urea levels. The animals exposed to aluminum showed higher lipid and protein oxidation in all the organs analyzed. In relation to the enzymes involved in antioxidant defense, the lungs showed lower superoxide dismutase (SOD) and catalase activity and a lower reduced and oxidized glutathione (GSH/GSSG) ratio. In the liver, aluminum administration led to a decrease in catalase activity and the GSH/GSSG ratio. Lower catalase activity was observed in the small intestine, as well as in the lungs and liver. In addition to alterations in antioxidant defense, increased levels of the chemokine CCL-2 were observed in the lungs, lower levels of IL-10 in the liver and small intestine, and decreased levels of IL-6 in the intestine of the animals that received aluminum hydroxide for 6 months. Long-term exposure to aluminum promoted steatosis in the liver. In the kidneys, mice treated with aluminum presented a decreased glomerular density than in the naive control group. In the small intestine, exposure caused villi shortening. Our results indicate that long-term oral administration of aluminum hydroxide provokes systemic histological damage, inflammation, and redox imbalance.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke.

The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237-0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity. However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

Changes in serum hypoxia-inducible factor-1α and erythropoietin in allergic rhinitis patients: Correlation with the Th inflammatory profile and disease comorbidities.

The balance between proinflammatory IFN-γ Th1 vs. the anti-inflammatory allergy-mediating IL-4-heralded Th2 reactions is pivotal in IgE-mediated allergic rhinitis (AR). Hypoxia-Inducible Factor (HIF)-1α is inducible by hypoxia and various cytokines. HIF-1α activates different anti-pathogen and allergic immune cells. This cross-sectional study assessed the changes in serum HIF-1α and its dependent erythropoietin (EPO) levels among hospital-characterized AR patients. Type of the immune reaction, Th1 vs. Th2, was stratified based on the calculated IL-4/IFN-γ direct ratio, after being measured using specific ELISA assays. 147 AR patients (83 males/64 females), and age-, BMI-, and gender-matched 24 healthy controls (13 males/11 females) were sequentially enrolled at ENT Unit, Prince Muteb General Hospital, Sakaka, Saudi Arabia. Measurement of serum parameters was carried out using specific ELISA assays. Contrary to the majority of previous publications, all controls and the majority of patients (n = 137/147) exhibited naive Th0 immune response. IFN-γ and HIF-1α levels were greater in controls than in patients (168.9 ± 173.9 vs 108 ± 94.5pg/mL; p<.012) and controls had a lower IL-4/IFN-ratio (2.439 ± 0.897 vs 3.33 ± 1.19; p<.001) than patients. The HIF-1α results disagree with earlier studies. Due to the wide inter-individual variations, serum IL-4 and EPO levels in controls were non-significantly higher than patients. Lower IL-4 levels (267.3 ± 79.95 vs 353.4 ± 320.6pg/mL; p < .01) and the ratio (2.814 ± 1.335 vs 3.431 ± 1.137; p < .05) were associated with obstructive sleep apnea. Lower ratio was also associated with inferior turbinate hypertrophy (3.051 ± 1.026 vs 3.787 ± 1.310; p < .001). EPO and IL-4 levels were lower in patients with deviated nasal septum (66.69 ± 26.81 vs 84.24 ± 61.5pg/mL; p < .021; and 299.5 ± 137.3 vs 391.1 ± 52.780pg/mL; p < .001, respectively). Significant correlations were found between the recorded levels and AR comorbidities. These results confirmed a pathogenic implication for HIF-1α and IFN-γ in AR that warranted future bigger and longitudinal studies.

Catalase and interleukin-6 serum elevation in a prediction of treatment-resistance in male schizophrenia patients.

Oxidative stress (OS) and neuroinflammatory pathways play an important role in the pathophysiology of schizophrenia. The present study investigated the relationship between OS, inflammatory cytokines, and clinical features in male patients with treatment-resistant schizophrenia (TRS). We measured plasma OS parameters, including manganese-superoxide dismutase (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD), total-SOD (T-SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px); and serum inflammatory cytokines, including interleukin (IL)-1α, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)-γ, from 80 male patients with chronic schizophrenia (31 had TRS and 49 had chronic stable schizophrenia (CSS)), and 42 healthy controls. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale (PANSS). Compared with healthy controls, plasma Mn-SOD, CuZn-SOD, T-SOD, GSH-Px, and MDA levels were significantly lower, while CAT and serum IL-6 levels were higher in both TRS and CSS male patients (all P<0.05). Significant differences in the activities of CAT (F = 6.068, P=0.016) and IL-6 levels (F = 6.876, P=0.011) were observed between TRS and CSS male patients after analysis of covariance. Moreover, a significant positive correlation was found between IL-6 levels and PANSS general psychopathology subscores (r=0.485, P=0.006) and between CAT activity and PANSS total scores (r=0.409, P=0.022) in TRS male patients. CAT and IL-6 levels were predictors for TRS. Additionally, in chronic schizophrenia patients, a significant positive correlation was observed between IL-6 and GSH-Px (r=0.292, P=0.012), and the interaction effect of IL-6 and GSH-Px was positively associated with PANSS general psychopathology scores (r=0.287, P=0.014). This preliminary study indicated that variations in OS and inflammatory cytokines may be involved in psychopathology for patients with chronic schizophrenia, especially in male patients with TRS.

HPLC/MS characterization of Syzygium aromaticum L. and evaluation of its effects on peritoneal adhesion: Investigating the role of inflammatory cytokines, oxidative factors, and fibrosis and angiogenesis biomarkers.

The dried flower bud of Syzygium aromaticum L. (S. aromaticum) (Myrtaceae), cloves, have been used for their analgesic and anti-inflammatory activities. Peritoneal adhesion (PA) is the most common complication of abdominal and pelvic surgeries, which causes significant adverse effects and severe economic burden. The present study aimed to evaluate the preventive effect of S. extract (SAE) on PA formation in a rat model. Male Wistar 8-week-old rats were randomly divided into sham, control (received vehicle), and treatment (0.25%, 0.5%, and 1% w/v of SAE) groups. The adhesion and related factors were examined using the Nair scoring system and immunological and biochemical kits for the levels of inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α], growth factors [transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)], oxidative [nitric oxide (NO) and malondialdehyde (MDA)], and anti-oxidative [glutathione (GSH)] factors. Our results figured out that the adhesion score and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly increased, but the GSH level was decreased in the control group compared to the sham group (p< 0.001-0.05). On the other hand, the 0.25% SAE group had a lower adhesion score, and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly decreased compared with the vehicle group, and the level of GSH was increased (p< 0.001-0.05). SAE could efficiently reduce adhesion score and regulate inflammatory cytokines, oxidative and anti-oxidative factors, and biomarkers of fibrosis and angiogenesis. Therefore, clove extract can be considered a potential candidate for PA management.