Differences In IL-6 Research Articles

Effect of continuous positive airway pressure therapy on blood levels of IL-6, IL-10, IL-18, IL-1β, IL-4, and IL-17 in obstructive sleep apnoea adults: A systematic review, meta-analysis and trial sequential analysis

Obstructive sleep apnoea (OSA) is a long-term disorder characterized by frequent blockages in the upper respiratory tract during sleep, often leading to abrupt awakenings, with or without a decrease in oxygen levels. The systematic review and meta-analysis aimed to assess the effect of continuous positive airway pressure therapy (CPAP) on blood interleukin (IL) levels of IL-6, IL-10, IL-18, IL-1β, IL-4, and IL-17 in OSA adults. The published databases from PubMed, Scopus, Web of Science, and Cochrane Library were searched from 2003 to 2024, without any restrictions. The Review Manager software 5.3 was employed to compute effect sizes, which were presented as the standardized mean difference (SMD) along with a 95% confidence interval (CI). In total, 320 records were identified through database searching; ultimately, 42 articles were included in the qualitative synthesis and then the meta-analysis. The CPAP therapy significantly reduces IL-6 levels, as indicated SMD=0.64 [95% CI: 0.35, 0.93] and P<0.0001. CPAP therapy significantly reduced IL-18 and IL-1β levels in adults with OSA, but there is no significant difference in IL-10, IL-4, or IL-17 levels. Age, blood sample, body mass index, ethnicity, and treatment duration for IL-6 and apnoea-hypopnea index with IL-10 levels were effective factors in the pooled results. Experimentally, there was an interaction between IL-18 and IL-1β. CPAP therapy has a positive impact on inflammatory markers in OSA adults; remarkably, it reduces IL-6 and IL-1β levels. Nevertheless, more evidence (such as the role of ethnicity) and understanding of interactions are needed.

Estimation of IL-8 and TNF-α Levels in Pediatric Diarrhea Patients Infected with Enterohemorrhagic E. coli O157:H7

Abstract Background: Verotoxins are bacterial virulence factors produced by E. coli O157:H7, transmitted by the fecal-oral route. Objectives: The aim of this article was to diagnose E. coli O157:H7 which causes diarrhea and sometimes develops into HUS, which considers pig health problems and estimates the levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α in the sera of pediatric patients infected with Enterohemorrhagic E. coli compared to the control group. Materials and Methods: Stool and blood samples were collected from 421 pediatric patients with diarrhea, ranging in age from birth to 13 years old, from March to October 2022. Samples were collected from Al Noor Teaching Hospital, Babylon Hospital for Pediatric and Gynecology, Hilla, Iraq. E. coli O157:H7 was cultured on eosin methylene blue (EMB) and Sorbitol MacConkey agar (SMA), confirmed by biochemical test and cultured on HiCrome E. coli O157:H7 selective medium which was an agar base supplemented with cefixime tellurite agar. Serum from 30 pediatric diarrhea patients infected with E. coli O157:H7 compared with 30 healthy children as control group used to determine serum levels of IL-8 and TNF-α by sandwich ELISA. Results: The results revealed that out of the total 421 samples used in this study, E. coli O157H:7, represented 7% (30 of 421) stool samples. This 30serum samples of infected children as well as 30 samples from healthy children subjected to the estimate serum level of IL-8 and TNF-α which record significant differences P ≤ 0.01 and P ≤ 0.05 to this cytokines in different age group; the mean of IL-8 level was 283.62 ± 17.8 pg/mL (7–9 years), and the mean of TNF-α was 208.62 ± 28.7 pg/mL (10–13 years) comparative with the control group of 80.58 ± 15.4pg/mL and 32.50 ± 7.5 pg/mL, respectively, and also result showed an increased mean level of IL-8 than TNF-α in the male comparative with female 195.19 ± 10.4 pg/mL and 159.05 ± 12.4 pg/mL, respectively, comparative with the control group. The result showed no significant differences in IL-8 and TNF-α between watery diarrhea (192.43 ± 24.3 pg/mL and 136.05 ± 20.4 pg/mL) and bloody diarrhea (189.02 ± 22.5 pg/mL and 123.80 ± 13.5 pg/mL), and also result showed significant increase of mean sera level of IL-8 than TNF-α in formula feeding children comparative with breastfeeding children (187.87 ± 19.5 pg/mL and 119.93 ± 17.4 pg/mL, respectively). Conclusion: The finding of this study suggested that increased levels of IL-8 and TNF-α are present in all age groups, in male comparative with female, and also in pediatric diarrhea feeding by formula than breastfeeding and no differences of this cytokine according to consistency of diarrhea. These results contribute to using the immune profile as a serological marker for diagnosing diarrhea caused by E. coli O157:H7 in comparison with the control group.

Effect of aspirin combination/clopidogrel combination on high-sensitivity C-reactive protein and P-selectin levels in patients with acute coronary syndrome

Purpose: To investigate the effect of combining aspirin with clopidogrel on high-sensitivity C-reactive protein (hs-CRP) and P-selectin in patients with acute coronary syndrome (ACS). Methods: The medical records of 198 ACS patients treated at Zhaotong Traditional Chinese Medicine Hospital, Zhaotong, China between January 2022 and January 2023 were analyzed retrospectively. Control group (88 patients) received aspirin (300 mg once, and subsequently a maintenance dose of 100 mg daily for 6 months), while the study group (118 patients) received the same dose of aspirin and clopidogrel (150 mg once, and a maintenance dose of 75 mg daily for 6 months). Levels of P-selectin, interleukin-6 (IL-6), hs-CRP, IL-8, tumor necrosis factor-α (TNF-α), efficacy, and incidence of adverse reactions in both groups were determined. Results: There was no significant difference in P-selectin and hs-CRP levels between the two groups before treatment (p &gt; 0.05). However, P-selectin and hs-CRP levels in the study group decreased significantly compared to control group (p &lt; 0.0001). Similarly, there was no significant difference in IL-8, IL-6 and TNF-α levels between the two groups before treatment (p &gt; 0.05). However, IL-8, IL-6, and TNF-α reduced significantly after treatment (p &lt; 0.0001), with more significantly lower levels observed in the study group (p &lt; 0.001). There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: Aspirin combined with clopidogrel significantly lowers P- selectin, and hs-CRP, IL-8, IL-6, and TNF-α levels without worsening adverse reactions. A more comprehensive analysis of the combined use of aspirin with clopidogrel including all the associated mechanisms in the treatment of ACS is necessary.

Impact of Bifidobacterium longum1714® on maternal cytokine response in peripheral blood mononuclear cells

PurposeThe maternal immune system is implicated in adverse pregnancy outcomes. Manipulation of maternal immune response by probiotics holds potential to reduce pregnancy complications. The MicrobeMom2 study investigates the impact of probiotic supplementation on maternal immune responses to pathogen associated molecular patterns (PAMPs) in peripheral blood mononuclear cells (PBMCs) during pregnancy. MethodsThis double-blinded randomised-controlled trial involved oral supplementation of Bifidobacterium longum subsp. longum 1714® (B. longum 1714; daily ingestion of a minimum of 1x109 colony forming units) or placebo from 16 to 20-weeks’ gestation until delivery in healthy pregnant women. The primary outcome was a change in IL-10 production, after stimulation with Lipopolysaccharide (LPS) or anti-CD3/28/2, in PBMCs isolated from blood samples taken at baseline (11–15 weeks’ gestation) and late pregnancy (28–32 weeks’ gestation) after 48 h incubation. 68 subjects were needed (34ineachgroup) for 80 % power at an alpha significance of 0.05 to detect differences in IL10. Results72 women (mean ± SD age 33.17 ± 4.53 years and median (25th, 75th centile) body mass index 24.93 (21.93, 27.57 kg/m2)) were recruited with primary outcome data. Using LPS, late pregnancy fold change in IL-10 in PBMCs after 48 h incubation was median (25th, 75th centile) 88.45 (4.88, 488.78) in the intervention, 24.18 (6.36, 141.17) in the control group, p = 0.183. Using anti-CD3/28/2, values were 189.69 (425.96, 866.57),148.74 (31.67, 887.03) in intervention and control groups, respectively, p = 0.506. No significant differences were observed between the two groups. ConclusionMaternal antenatal supplementation with B. longum 1714 did not alter cytokine production by maternal PBMCs in response to PAMPs or anti-CD3/28/2.Trial registration number: ISRCTN registry ISRCTN43013285.

The Application of Gait Speed and Grip Strength As a Frailty Screening Tool in Elderly Patients with Mulitiple Myeloma

Introduction Gait speed and grip strength are easily obtainable objective measures of physical function, they are important diagnostic parameters for sarcopenia, and also representative geriatric index of frailty and function that performed well, even compared with more comprehensive frailty assessments. Brief screening tests for frailty that can easily fit into the clinic workflow and predict important clinical outcomes are needed. Geriatric assessment (GA) of the International Myeloma Working Group (IMWG) applying to the newly diagnosed MM, because of its subjectivity and relative complexity, obstructing widespread development in clinical. The purpose of our analysis was to examine the potential value of gait speed or grip strength as a screening test for frailty in elderly patients with MM. At the same time, efforts are ongoing to explore the significance of dynamic evaluation . Methods All 47 patients aged 60 years and older who presented for an initial consultation in our hospital were eligible for participation. Gait speed and grip strength and IMWG-GA were measured in all consented patients. Gait speed was obtained using the National Institutes of Health 4-m gait speed test, while grip strength was measured using a Hand Dynamometer. And the differences in SASP (Senescent Associated Secretory Phenotype) between different gait speed groups were compared. Results All enrolled patients underwent dynamic evaluation and completed 124 frequency IMWG-GA, 131 gait speed and 129 grip strength tests. IMWG-GA: fit group: 43.5%(54/124), intermediate fit: 7.3%(9/124), frail: 49.2%(61/124). Gait speed &amp;lt;0.8m/s: 53.4%(70/131), ≥0.8m/s：46.6%(61/131). Grip strength：Male group：&amp;lt;28kg group 51.5%(50/97), ≥28kg group 48.5%(47/97); Female group: &amp;lt;18kg group 59.4%(19/32), ≥18kg group 40.6%(13/32). Complete and analyzable data from all cases showed high consistency between gait speed and IMWG-GA (AUC=0.83), the “4-m gait speed test” can be used as an effective predictor for frailty. And between grip strength and IMWG-GA (AUC=0.68), “Grip strength ”can also be used as an effective predictor for frailty, but its performance seems to be slightly inferior to“ 4-m gait speed test ”. The combination of “4-m gait speed test” and “grip strength” can serve as an effective predictor for IMWG-GA(AUC=0.74), and its seems to be superior to using “4-m gait speed test” or “grip strength” alone. The incidence rate of sarcopenia is 49%(23/47). We further analyzed and found that, the differential expression of IL-6 (38.51±17.59 vs 8.09±3.97 pg/ml, p&amp;lt;0.05) and IFN-γ(2.0±0.49 vs 0.86±0.14 pg/ml, p&amp;lt;0.05) in SASP between the two groups with a gait speed of &amp;lt;0.8m/s and ≥0.8m/s. While there was no statistically significant difference in IL-8 and IL-1b between the two groups. We conducted a dynamic evaluation of IMWG-GA and gait speed and grip strength. As the number of treatment courses increases and the treatment effect becomes apparent, the proportion of patients with frail decreases and the proportion of patients with improved gait increases, while the difference in grip strength changes is not significant(Figure1-3). Conclusions In summary, gait speed and grip strength have strong diagnostic value in evaluating elderly frailty MM, and dynamic monitoring is simple and feasible in clinical practice. The relationship between sarcopenia and frailty, as well as the role of dynamic assessment, still needs further exploration.

T regulatory lymphocytes specific for SARS-CoV-2 display increased functional plasticity

The study of phenotypic and functional characteristics of immune cells involved in host response to SARS-CoV-2 is relevant for understanding COVID-19 pathogenesis and individual differences in disease progression. We have analyzed chemokine receptor expression in SARS-CoV-2-specific CD4+ T lymphocytes from vaccinated donors, and have found an increase of CCR9+ and CCR6+ cells. CCR9+ specific CD4+ cells are enriched in T regulatory (Treg) lymphocytes. These cells specifically show heterogeneous regulatory activity, associated with different profiles of CCR9/CCR6 expression, individual differences in IL-10 and IL-17 production, and variable FoxP3 and Notch4 expression. A higher heterogeneity in FoxP3 is selectively observed in convalescent individuals within vaccinated population. Accordingly, SARS-CoV-2-specific CD4+ lymphocytes from COVID-19 patients are also enriched in CCR9+ and CCR6+ cells. CCR6+ specific Treg lymphocytes are mainly increased in critically ill individuals, indicating a preferential role for these cells in lung injury pathogenesis. We provide experimental evidence for a SARS-CoV-2-specific Treg population with increased plasticity, which may contribute to the differential pathogenic response against SARS-CoV-2 among individuals, and underlie the development of autoimmune conditions following SARS-CoV-2 infection.

Eucalyptus oil as adjuvant therapy for coronavirus disease 19 (covid-19): a randomized clinical trial

Link of Video Abstract: https://youtu.be/WzYiDQR2RvA Introduction: The coronavirus disease 19 (COVID-19) vaccination scheme is still being implemented worldwide, but problems with stock availability and other factors are still impeding this endeavor, especially in developing nations like Indonesia. Ethnopharmacology is known to provide a good source of a cheap candidate for anti-inflammation drugs. This study was conducted to determine the effectiveness of affordable adjuvant therapy, Eucalyptus oil, which has been used as a household remedy for respiratory tract infections in Indonesia. Methods: 52 mild-moderate COVID-19 patients were randomly assigned for a prospective clinical trial. A group of 26 patients was given standard COVID-19 treatment as a control group, while another 26 patients as the treated group were given standard therapy and use Eucalyptus oil as an adjuvant. The clinical sign and symptoms, cytokines interleukin (IL) 6, IL-10, and transforming growth factor-beta (TGF-β) profiles were recorded during the study period. Result: There was a trend of better improvement of clinical symptoms among patients who received adjuvant treatment than the control group. Altered smell (p = 0.003) and cough (p = 0.641) recovered faster in the treated group. While there was no marked difference in IL-10 and TGF-β levels among both groups, IL-6 level in the treated group was significantly lower and the neutrophil-to-lymphocyte ratio (NLR) was significantly decreased (p &lt; .05) than the control. Conclusion: Using Eucalyptus oil as an adjuvant of COVID-19 treatment promotes faster recovery of mild-moderate COVID-19 patients, probably via inhibition of the IL-6-mediated inflammation process.

Detection of Anti-ZIKV NS1 IgA, IgM, and Combined IgA/IgM and Identification of IL-4 and IL-10 as Potential Biomarkers for Early ZIKV and DENV Infections in Hyperendemic Regions, Thailand.

The frequency of Zika virus (ZIKV)-specific IgA and IgM and the cytokine expression profile of ZIKV-infected patients in hyperendemic areas remain unclear. This study investigated the rates of ZIKV non-structural protein 1 (NS1)-specific IgA and IgM and evaluated serum cytokine levels of ZIKV and Dengue virus (DENV) cases in Thailand to identify potential diagnostic biomarkers, elucidate the immunity against ZIKV and DENV, and investigate the association between cytokine levels and ZIKV symptoms. Low rates of positivity for ZIKV NS1-specific IgA and IgM were detected in our study. ZIKV NS1 IgA/M (11%, 11/101) in combination was more frequently detected than ZIKV NS1 IgM (2%, 2/101) or ZIKV NS1 IgA (4%, 4/96) alone, especially in acute ZIKV cases with previous DENV exposure (14%, 10/72). Cytokine analysis showed that both ZIKV and DENV infections induced polyfunctional immunity, and the latter triggered more prolonged responses. The existence of significant differences in IL-4 and IL-10 levels between acute ZIKV and acute DENV cases suggested that IL-4 (p = 0.0176) and IL-10 (p = 0.0003) may represent biomarkers for acute ZIKV and acute DENV infections, respectively. Analysis of the association between increased cytokine levels and ZIKV symptoms indicated that CXCL10 (p = 0.0029) was associated with exanthema, while IL-5 (p = 0.0496) was linked to headache. The detection of ZIKV NS1 IgA and IgM in combination may enhance the diagnosis of early ZIKV infection, particularly when levels of IgM or IgA alone are low or undetectable. IL-4 and IL-10 may serve as targets for the development of diagnostic tools to detect ZIKV and DENV infections early, respectively, in flavivirus-endemic regions.

An Investigation of Latex Sensitivity and Respiratory Complaints in Workers in a Rubber-Based Material Manufacturing Industry.

To present study aimed to investigate the prevalence of latex sensitivity in a workplace that produced rubber-based vehicle seals. The serum latex-specific IgE levels, respiratory complaints, PFT, serum interleukin (IL)-4, IL-5, IL-8, IL-10, IL-13 levels of all male workers (n = 108) exposed to latex in the workplace, which produced rubber seals, were compared with the control group (n = 52). The rates of latex-specific IgE >0.10 kU/L in the workers and control group were 12.3% and 4.1%, respectively ( P = 0.147). There was no difference in IL-4, IL-5, IL-10, and IL-13 levels between latex-specific IgE-positive, and -negative participants. Latex sensitivity was higher in workers who used rubber as a raw material than in the control group but it was not statistically significant.

Sex differences exist in adult heart group 2 innate lymphoid cells

BackgroundGroup 2 innate lymphoid cells (ILC2s) are the most dominant ILCs in heart tissue, and sex-related differences exist in mouse lung ILC2 phenotypes and functions; however, it is still unclear whether there are sex differences in heart ILC2s.ResultsCompared with age-matched wild-type (WT) male mice, 8-week-old but not 3-week-old WT female mice harbored an obviously greater percentage and number of heart ILC2s in homeostasis. However, the percentage of killer-cell lectin-like receptor G1 (Klrg1)− ILC2s was higher, but the Klrg1+ ILC2s were lower in female mice than in male mice in both heart tissues of 3- and 8-week-old mice. Eight-week-old Rag2−/− mice also showed sex differences similar to those of age-matched WT mice. Regarding surface marker expression, compared to age-matched male mice, WT female mice showed higher expression of CD90.2 and Ki67 and lower expression of Klrg1 and Sca-1 in heart total ILC2s. There was no sex difference in IL-4 and IL-5 secretion by male and female mouse heart ILC2s. Increased IL-33 mRNA levels within the heart tissues were also found in female mice compared with male mice. By reanalyzing published single-cell RNA sequencing data, we found 2 differentially expressed genes between female and male mouse heart ILC2s. Gene set variation analysis revealed that the glycine, serine and threonine metabolism pathway was upregulated in female heart ILC2s. Subcluster analysis revealed that one cluster of heart ILC2s with relatively lower expression of Semaphorin 4a and thioredoxin interacting protein but higher expression of hypoxia-inducible lipid droplet-associated.ConclusionsThese results revealed greater numbers of ILC2s, higher expression of CD90.2, reduced Klrg1 and Sca-1 expression in the hearts of female mice than in male mice and no sex difference in IL-4 and IL-5 production in male and female mouse heart ILC2s. These sex differences in heart ILC2s might be due to the heterogeneity of IL-33 within the heart tissue.

Biological determinants of blood-based cytokines in the Alzheimer's disease clinical continuum.

Converging translational and clinical research strongly indicates that altered immune and inflammatory homeostasis (neuroinflammation) plays a critical pathophysiological role in Alzheimer's disease (AD), across the clinical continuum. A dualistic role of neuroinflammation may account for a complex biological phenomenon, representing a potential pharmacological target. Emerging blood-based pathophysiological biomarkers, such as cytokines (Cyt) and interleukins (ILs), have been studied as indicators of neuroinflammation in AD. However, inconsistent results have been reported probably due to a lack of standardization of assays with methodological and analytical differences. We used machine-learning and a cross-validation-based statical workflow to explore and analyze the potential impact of key biological factors, such as age, sex, and apolipoprotein-E (APOE) genotype (the major genetic risk factor for late-onset AD) on Cyt. A set of Cyt was selected based on previous literature, and we investigated any potential association in a pooled cohort of cognitively healthy, mild cognitive impairment (MCI), and AD-like dementia patients. We also performed explorative analyses to extrapolate preliminary clinical insights. We found a robust sex effect on IL12 and an APOE-related difference in IL10, with the latter being also related to the presence of advanced cognitive decline. IL1β was the variable most significantly associated with MCI-to-dementia conversion over a 2.5year-clinical follow-up. Although preliminary, our data support further clinical research to understand whether plasma Cyt may represent reliable and noninvasive tools serving the investigation of neuroimmune and inflammatory dynamics in AD and to foster biomarker-guided pathway-based therapeutic approaches, within the precision medicine development framework.

023 Lenabasum, a cannabinoid type 2 receptor agonist, exerts anti-inflammatory effects in dermatomyositis in Th1 cells

Dermatomyositis (DM) is a chronic, systemic autoimmune disease affecting the skin, muscle, and lungs. Lenabasum, a non-psychoactive cannabinoid type 2 receptor (CB2R) agonist, is currently being investigated as a non-immunosuppressive treatment option for DM. The activation of CB2R has been shown to reduce several key pro-inflammatory cytokines implicated in DM. Our lab has previously demonstrated via immunohistochemistry (IHC) that Lenabasum decreases CD4, IFNβ, IFNγ and IL31 expression in DM skin at 12 weeks (p<0.05), with no differences in IL4 compared to placebo (p>0.05). In this study, we then utilized multiplexed flow cytometry of leukocytes eluted from DM skin to further analyze the expression of CB2R on 12 cell lineages. When evaluating cell lineages, CD4 T helper (Th) subsets were gated on CD4+ IFNγ+ Th1 and CD4+IL4+ Th2. There was a significantly higher frequency of parent (FOP) percentage (p<0.05) of CB2R in Th1 (61.05%, n=6) versus Th2 cells (25.5%, n=6). Among myeloid cell lineages, there was greater FOP of CB2R in M2 macrophages (CD68+CD163+), CD14++CD16++ macrophages, and monocyte derived dendritic cells (moDCs; CD11c+CD14+). With 15mmol of Lenabasum, there was a trend towards a decrease of: TNFα in M2 macrophages; IFNγ and IFNβ in CD4+ Tcells; IFNβ in CD16+ cells; and IL31 in Th1 cells, CD14++CD16+ macrophages, and M2 macrophages. There was also a significant decrease in moDCs secreting IL31 with Lenabasum (p<0.01). Imaging mass cytometry of untreated DM skin demonstrated the highest IL31 MPI in moDCs. IL31 was also elevated to a lesser extent in other myeloid cell lineages. These data suggest Lenabasum may exert specific anti-inflammatory effects in DM, particularly on Th1 cells and Th1-derived IL31.

Inflammation-related molecules in tears of patients with chronic ocular pain and dry eye disease

The purpose of this study was to analyze inflammation- and pain-related molecules in tears of patients suffering from chronic ocular pain associated with dry eye (DE) and/or a previous corneal refractive surgery (RS). Based on history, symptomatology, and clinical signs, the subjects (n = 180, 51.0 ± 14.7 years, 118 females, 62 males) in this cross-sectional study were assigned to one of five groups: DE and chronic ocular pain after RS (P/DE-RS, n = 52); asymptomatic subjects, i.e., without DE and chronic ocular pain, after RS (A-RS, n = 30); DE and chronic ocular pain without previous RS (P/DE-nonRS, n = 31); DE, no pain, and no previous RS (DE-nonRS, n = 35); and asymptomatic subjects with no previous RS (controls, n = 32). The tear concentrations of 20 cytokines and substance P (SP) were analyzed by immunobead-based assay and enzyme-linked immunosorbent assay, respectively. We found that tear levels of interleukin (IL)-10 and SP were increased in the RS groups. There were significant differences in IL-8/CXCL8 among the five groups. Nerve growth factor (NGF) tear levels were significantly higher in P/DE-RS than in DE-nonRS and controls. IL-9 had the highest percentage of detection in the P/DE-RS and P/DE-nonRS groups, while macrophage inflammatory protein (MIP)-1α, IL-2, and interferon (IFN)-γ were higher in the P/DE-RS, A-RS, and P/DE-nonRS groups. IL-17A was detected only in the A-RS group. Moderate correlations were observed in the A-RS, P/DE-nonRS, DE-nonRS and controls groups. A positive correlation was obtained between growth related oncogene concentration and tear break-up time (rho = 0.550; p = 0.012), while negative correlation was found between monocyte chemoattractant protein-3/CCL7 and conjunctival staining (rho = −0.560; p = 0.001), both in the A-RS group. IL-10 correlated positively with ocular pain intensity (rho = 0.513; p = 0.003) in the P/DE-nonRS group. Regulated on Activation Normal T Cell Expressed and Secreted/CCL5 correlated negatively with conjunctival staining (rho = −0.545; p = 0.001) in the DE-nonRS group. SP correlated negatively with corneal staining (rho = −0.559; p = 0.001) in the controls. In conclusion, chronic ocular pain was associated with higher IL-9 tear levels. IL-10, SP, MIP-1α/CCL3, IL-2, and IFN-γ were associated with previous RS. Higher levels of IL-8/CXCL8, MIP-1α/CCL3, IL-2, and IFN-γ were associated with DE-related inflammation, while NGF levels were related to chronic ocular pain and DE in RS patients. These findings suggest that improved knowledge of tear cytokines and neuromodulators will lead to a more nuanced understanding of how these molecules can serve as biomarkers of chronic ocular pain, leading to better therapeutic and disease management decisions.

Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis

Despite available diagnostic tests and recent advances, diagnosis of pulmonary invasive aspergillosis (IPA) remains challenging. We performed a longitudinal case-control pilot study to identify host-specific, novel, and immune-relevant molecular candidates indicating IPA in patients post allogeneic stem cell transplantation (alloSCT). Supported by differential gene expression analysis of six relevant in vitro studies, we conducted RNA sequencing of three alloSCT patients categorized as probable IPA cases and their matched controls without Aspergillus infection (66 samples in total). We additionally performed immunoassay analysis for all patient samples to gain a multi-omics perspective. Profiling analysis suggested LGALS2, MMP1, IL-8, and caspase-3 as potential host molecular candidates indicating IPA in investigated alloSCT patients. MMP1, IL-8, and caspase-3 were evaluated further in alloSCT patients for their potential to differentiate possible IPA cases and patients suffering from COVID-19-associated pulmonary aspergillosis (CAPA) and appropriate control patients. Possible IPA cases showed differences in IL-8 and caspase-3 serum levels compared with matched controls. Furthermore, we observed significant differences in IL-8 and caspase-3 levels among CAPA patients compared with control patients. With our conceptual work, we demonstrate the potential value of considering the human immune response during Aspergillus infection to identify immune-relevant molecular candidates indicating IPA in alloSCT patients. These human host candidates together with already established fungal biomarkers might improve the accuracy of IPA diagnostic tools.

Alterations in T-Cell Transcription Factors and Cytokine Gene Expression in Late-Onset Alzheimer's Disease.

Late-onset Alzheimer's disease (LOAD) is associated with many environmental and genetic factors. The effect of systemic inflammation on the pathogenesis of neurodegenerative diseases such as AD has been strongly suggested. T helper cells (Th) are one of the important components of the immune system and can easily infiltrate the brain in pathological conditions. The development of each Th-subset depends on the production of unique cytokines and their main regulator. This study aimed to compare the mRNA levels of Th-related genes derived from peripheral blood mononuclear cells of LOAD patients with control. Also, the identification of the most important Th1/Th2 genes and downstream pathways that may be involved in the pathogenesis of AD was followed by computational approaches. This study involved 30 patients with LOAD and 30 non-demented controls. The relative expression of T-cell cytokines (IFN-γ, TNF-α, IL-4, and IL-5) and transcription factors (T-bet and GATA-3) were assessed using Real-time PCR. Additionally, protein-protein interaction (PPI) was investigated by gene network construction. A significant decrease at T-bet, IFN-γ, TNF-α, and GATA-3 mRNA levels was detected in the LOAD group, compared to the controls. However, there was no significant difference in IL-4 or IL-5 mRNA levels. Network analysis revealed a list of the highly connected protein (hubs) related to mitogen-activated protein kinase (MAPK) signaling and Th17 cell differentiation pathways. The findings point to a molecular dysregulation in Th-related genes, which can promising in the early diagnosis or targeted interventions of AD. Furthermore, the PPI analysis showed that upstream off-target stimulation may involve MAPK cascade activation and Th17 axis induction.

Predicting the risk of left ventricular diastolic dysfunction in obesity

Obesity may develop heart failure with preserved ejection fraction, which is based on left ventricular diastolic dysfunction (LV DD). Currently, the search for effective predictors of LV DD is extremely relevant.Aim. To assess the prognostic value of key and additional metabolic risk factors (RFs), neurohumoral and profibrotic factors in the development of LV DD in obese patients.Material and methods. The study included 149 men with general obesity. The mean age was 49,7±7,9 years. The inclusion criteria was the presence of class I-III general obesity. The average body mass index was 32,9±3,6 kg/m2. The exclusion criteria were hypertension, coronary atherosclerosis, type 2 diabetes, as well as LV DD according to transthoracic echocardiography. Depending on the presence of epicardial adiposity, patients were divided into two groups: group 1 — epicardial adipose tissue (EAT) thickness ≥7 mm (n=70), group 2 — EAT &lt;7 mm (n=31). In all patients, the following laboratory parameters were determined in blood serum using enzyme immunoassay: type I and III collagen, Procollagen I C-Terminal Propeptide (PICP), matrix metalloproteinase-3 (MMP-3), transforming growth factor β1, vascular endothelial growth factor, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, C-reactive protein (CRP), adiponectin, soluble leptin receptor, leptin, lipid parameters and free fatty acids (FFA). After 4,7±0,3 years, echocardiography was repeated in order to assess LV diastolic function.Results. Comparative analysis of metabolic risk factors revealed a significant increase in the level of total cholesterol (p=0,001), low-density lipoprotein cholesterol (LDL-C) (p&lt;0,0001), triglycerides (TGs) (p&lt;0,0001). These groups had no differences in such parameters as high-density lipoprotein cholesterol (p=0,09) and glucose (p=0,12). An increase in the level of such pro-inflammatory cytokines as TNF-α (p&lt;0,0001), CRP (p&lt;0,0001), IL-6 (p&lt;0,0001) in group 1 was revealed, while differences in IL-10 (p=0,34) levels were not significant. In group 1, there was a significant increase in leptin levels (p&lt;0,0001), a decrease in levels of adiponectin (p&lt;0,0001) and leptin receptor (p=0,001). In group 1, an increase in the level of all studied profibrotic factors was revealed. After 4,7±0,3 years, repeated echocardiography revealed that selected groups were comparable in such parameters as A, E, E/A, E/e’, e’, and the peak tricuspid regurgitation velocity. There was a significant difference in left atrial volume index (p=0,0003). LV DD was detected in 20 patients. Binary logistic regression revealed the following most significant predictors of LV DD in obese patients: glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.Conclusion. Thus, the following most significant predictors of LV DD in obese patients were identified glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.

Predicting the risk of left ventricular diastolic dysfunction in obesity

Obesity may develop heart failure with preserved ejection fraction, which is based on left ventricular diastolic dysfunction (LV DD). Currently, the search for effective predictors of LV DD is extremely relevant.Aim. To assess the prognostic value of key and additional metabolic risk factors (RFs), neurohumoral and profibrotic factors in the development of LV DD in obese patients.Material and methods. The study included 149 men with general obesity. The mean age was 49,7±7,9 years. The inclusion criteria was the presence of class I-III general obesity. The average body mass index was 32,9±3,6 kg/m2. The exclusion criteria were hypertension, coronary atherosclerosis, type 2 diabetes, as well as LV DD according to transthoracic echocardiography. Depending on the presence of epicardial adiposity, patients were divided into two groups: group 1 — epicardial adipose tissue (EAT) thickness ≥7 mm (n=70), group 2 — EAT &lt;7 mm (n=31). In all patients, the following laboratory parameters were determined in blood serum using enzyme immunoassay: type I and III collagen, Procollagen I C-Terminal Propeptide (PICP), matrix metalloproteinase-3 (MMP-3), transforming growth factor β1, vascular endothelial growth factor, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, C-reactive protein (CRP), adiponectin, soluble leptin receptor, leptin, lipid parameters and free fatty acids (FFA). After 4,7±0,3 years, echocardiography was repeated in order to assess LV diastolic function.Results. Comparative analysis of metabolic risk factors revealed a significant increase in the level of total cholesterol (p=0,001), low-density lipoprotein cholesterol (LDL-C) (p&lt;0,0001), triglycerides (TGs) (p&lt;0,0001). These groups had no differences in such parameters as high-density lipoprotein cholesterol (p=0,09) and glucose (p=0,12). An increase in the level of such pro-inflammatory cytokines as TNF-α (p&lt;0,0001), CRP (p&lt;0,0001), IL-6 (p&lt;0,0001) in group 1 was revealed, while differences in IL-10 (p=0,34) levels were not significant. In group 1, there was a significant increase in leptin levels (p&lt;0,0001), a decrease in levels of adiponectin (p&lt;0,0001) and leptin receptor (p=0,001). In group 1, an increase in the level of all studied profibrotic factors was revealed. After 4,7±0,3 years, repeated echocardiography revealed that selected groups were comparable in such parameters as A, E, E/A, E/e’, e’, and the peak tricuspid regurgitation velocity. There was a significant difference in left atrial volume index (p=0,0003). LV DD was detected in 20 patients. Binary logistic regression revealed the following most significant predictors of LV DD in obese patients: glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.Conclusion. Thus, the following most significant predictors of LV DD in obese patients were identified glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.

Effects of high intensity interval training on cardiorespiratory fitness and salivary levels of IL-8, IL-1ra, and IP-10 in adults with asthma and non-asthma controls

Objective The purpose of this study was to determine whether high intensity interval training (HIIT) would lead to improvements in 1) maximal VO2, VE, VE/VCO2, and VE/MVV, and/or 2) resting salivary concentrations of pro-inflammatory markers Interleukin (IL-8), interferon-gamma-inducible-protein (CXCL10/IP-10)) and anti-inflammatory marker IL-1 receptor antagonist (IL-1ra) in adults with well-controlled asthma compared to non-asthma controls. Methods Participants completed a maximal exercise test at the beginning (T1) and end (T2) of a 6-week HIIT intervention; saliva samples were obtained at the beginning and 30 min following the first (T1) and last (T2) exercise session. Results Adults with asthma (n = 20; age: 21.4 ± 2.4 years) and non-asthma controls (n = 12; age: 22.5 ± 3.4 years) completed the intervention. VO2max increased from T1 to T2 in both groups (asthma T1 32.9 ± 8, T2 38.6 ± 8.2 ml/kg/min; controls T1 34.5 ± 11.8, T2 38.9 ± 12.3 ml/kg/min). VEmax also increased in both groups (asthma T1 97.7, T2 110.8 units, p < 0.001, hp 2 = <0.04; control T1 106.3, T2 118.1, p < 0.001, hp 2 0.02). An increase in VE/VCO2 (F(1, 10)=22.11, p = 0.001) and VE/MVV (F(1, 10) = 111.30, p < 0.001) was observed in the control group; no differences were observed in the asthma group. No differences in IL-8 or IL-1ra were observed between groups. In the asthma group, resting salivary IP-10 concentrations significantly decreased from T1 (0.025 pg/ug protein) to T2 (0.015 pg/ug protein, p = 0.039, hp 2 = 0.3 (moderate effect)). Conclusion A 6-week HIIT intervention led to a similar increase in VO2max and VEmax in those with and without asthma, and a decrease in resting salivary IP-10 levels among adults with asthma.

Analysis of clinical characteristics of patients with chronic critical illness after sepsis

To investigate the clinical characteristics of patients who develop chronic critical illness (CCI) after sepsis. The survival patients with sepsis admitted to the department of critical medicine of Baoan Central Hospital of Shenzhen for the first time from April 2019 to October 2020 were enrolled. According to clinical outcomes, patients were divided into CCI group [intensive care unit (ICU) stay ≥ 14 days, with persistent organ dysfunction] and rapid recovery (RAP) group. The baseline characteristic on admission and clinical outcomes of patients in the two groups were collected and compared. Blood samples were collected to measure serum interleukins (IL-6, IL-10) levels and peripheral blood lymphocyte count (LYM) count were obtained from all patients after admission. The differences of above indexes on the 1st, 7th and 14th day in ICU between the two groups were compared, the 180 day cumulative survival rate of the two groups was observed. (1) Twenty-two septic patients developed CCI and 28 patients with RAP were included. There were no significant differences in gender and infection site between the two groups. The age, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), proportion of septic shock, mechanical ventilation time, length of ICU stay, total length of hospital stay and proportion of secondary infection of CCI patients were higher than those in RAP group [age (years old): 61.0±13.8 vs. 50.3±13.9, proportion of patients aged ≥ 65 years old: 54.5% (12/22) vs. 25.0% (7/28), APACHE II score: 20.5±4.4 vs. 14.4±4.3, SOFA score: 10 (7, 12) vs. 5 (3, 8), septic shock ratio: 40.9% (9/22) vs. 17.9% (5/28), time of mechanical ventilation (days): 18.5 (12.0, 28.0) vs. 5.0 (3.0, 7.0), length of ICU stay (days): 26 (18, 46) vs. 8 (6, 12), total length of hospital stay (days): 31 (26, 51) vs. 14 (12, 17), secondary infection ratio: 72.7% (16/22) vs. 7.1% (2/28), all P < 0.05]. (2) The IL-6 levels of CCI group were higher than that of RAP group at all time points (ng/L: 176.86±103.54 vs. 113.32±71.34 on the 1st day, 84.72±46.06 vs. 54.98±26.61 on the 7th day, 44.28±20.20 vs. 17.76±4.70 on the 14th day, all P < 0.05). On the 1st and 7th day of admission, there were no significant differences in IL-10 and LYM levels between the two groups. On the 14th day of admission, IL-10 levels in CCI group were higher than that in RAP group (ng/L: 15.09±3.61 vs. 8.92±1.98, P < 0.05), while LYM was relatively lower [×109/L: 0.62 (0.43, 1.02) vs. 1.17 (0.93, 1.71), P < 0.05]. (3) The Log-Rank test results of Kaplan-Meier survival curve showed that the 180-day cumulative survival rate of CCI group was significantly lower than that of RAP group (63.6% vs. 96.4%, Log-Rank: χ2 = 9.024, P = 0.007). Septic patients with advanced age, high APAHCE II score and high SOFA score are prone to secondary CCI, resulting in long hospital stay, high secondary infection rate and poor prognosis. The occurrence of CCI may be related to the continuous expression of proinflammatory mediators and subsequent immunosuppression.

244 Fertility Outcomes Associated with Reproductive Tract Cytokines and Microbiota in Postpartum Beef Cows

Abstract Local immune activity in the reproductive tract is crucial in the response to uterine diseases, normal reproductive functions, and establishing pregnancy. Few studies have evaluated the influence of the local immune environment of the reproductive tract on fertility outcomes. The objectives were to 1) evaluate reproductive cytokine concentrations in postpartum cows undergoing estrus synchronization followed by timed artificial insemination (TAI) and 2) correlate reproductive bacterial communities with cytokine concentrations. Angus cows (n = 20) were subjected to a 7-Day Co-Synch protocol with pre-synchronization beginning 21 days prior (d -21) to TAI (d 0). Uterine and vaginal flushes were collected on d -21 and -2. Pregnancy was determined by transrectal ultrasound on d 30. Bacterial community profiling and analyses were conducted targeting the V1 to V3 hypervariable regions of the 16S rRNA gene. Cytokine concentrations for interleukin (IL)-1b, IL-6, IL-10, and transforming growth factor beta (TGF-β) were determined by commercial ELISA kits. Concentration data were analyzed using PROC MIXED and correlations using Pearson correlation in SAS. No differences were detected in vaginal samples (P &amp;gt;0.05). No differences in IL-10 or IL-1b concentrations were detected in uterine samples (P &amp;gt;0.05). Uterine TGF-β concentrations were greater in resulting pregnant than non-pregnant cows (44.0 ± 13.4 pg/mL vs 14.7 ± 4.9 pg/mL; P = 0.05). Uterine TGF-β was negatively correlated with the relative abundance of genera Treponema (r = -0.668; P = 0.05) in resulting non-pregnant cows on d -21. Uterine IL-6 concentrations were greater in resulting non-pregnant than pregnant cows (198.7 ± 21.8 pg/mL vs 144.3 ± 16.1 pg/mL; P = 0.05). Uterine IL-6 and the relative abundance of genera Butyrivibrio were positively correlated (r = 0.742; P = 0.02) in resulting non-pregnant cows on d -21. These results suggest possible relationships between uterine bacterial communities and cytokines prior to TAI that may ultimately affect fertility outcomes in beef cattle.