IL-10 Ratio Research Articles

Periodontitis Provokes Retinal Neurodegenerative Effects of Metabolic Syndrome: A Cross-Sectional Study

Background: This cross-sectional study aims to investigate the retino-choroidal degenerative effects of periodontitis, metabolic syndrome (Mets), and the combination of these diseases using optical coherence tomography (OCT) measurements. Methods: Ninety-two patients selected according to inclusion criteria were divided into four groups: systemically and periodontally healthy (control), systemically healthy periodontitis (PD), periodontally healthy metabolic syndrome (MetS), and periodontitis and metabolic syndrome combined (PD-MetS). The systemic inflammatory–oxidative effects of periodontitis and MetS were biochemically evaluated using the serum TNF-α level, IL-1β/IL-10 ratio, and oxidative stress index (OSI: TOS/TAS). Retinal (AMT, pRNFLT, and GCL + T) and choroidal (SFCT) morphometric measurements and vascular evaluations (foveal capillary density) were performed via OCT Angio with swept-source technology. Results: Both periodontitis and Mets cause systemic inflammatory stress characterized by significant increases in the IL-1β/IL-10 ratio and OSI (p < 0.05). Compared to the control group, the AMT was significantly thinner in the MetS group, the pRNFLT was significantly thinner in the PD-MetS group, and the SFCT was significantly thinner in both groups (p < 0.05). The GCL+ was slightly thicker in the Mets groups. (p > 0.05) Foveal capillary density did not differ significantly among the groups. (p > 0.05). Conclusions: Periodontitis-related inflammatory stress alone causes changes in retinal and subfoveal choroidal thicknesses that are not statistically significant. On the other hand, when combined with Mets, it may significantly provoke the retinal neurodegenerative effects of this disease.

Long-Term Physical Activity Mitigates Inflammaging Progression in Older Adults Amidst the COVID-19 Pandemic

Background: Inflammaging and physical performance were investigated in older adults before and after the COVID-19 pandemic. Methods: Older women (n = 18) and men (n = 7) (mean age = 73.8 ± 7.1) were evaluated before the COVID-19 pandemic (PRE), 12 months after the lockdown (POST), and 10 months after resuming exercise training (POST-TR). Physical tests [gait speed (GS) and timed-up-and-go (TUG)]; muscle strength (handgrip—HG); and serum cytokine levels were assessed. Results: Older women showed higher GS and TUG at POST than PRE and POST-TR but lower HG at POST-TR than PRE, whereas older men exhibited lower HG at POST and POST-TR than PRE. Both groups presented (1) lower IL-10 and IL-12p70 values in contrast to higher IL-6/IL-10 and IL-8/IL-10 ratios at POST than PRE; (2) higher IL-10 values and lower IL-8/IL-10 ratio at POST-TR than POST; (3) higher IL-12p70/IL-10 ratio at POST-TR than PRE and POST. Particularly, older women showed (4) lower IL-6 values at POST and POST-TR than PRE; (5) lower IL-8 and IL-10 values at POST-TR than POST; (6) and higher TNF-α/IL-10 and IFN-γ/IL-10 ratios at POST than PRE and POST-TR. Significant correlations between the variables were found in both groups. Discussion: During the COVID-19 pandemic, detraining and resumption of exercise training promoted distinct alterations in physical capacity and inflammaging among older women and older men.

Salivary assessment of the immune/inflammatory responses and oxidative stress in older adults vaccinated with CoronaVac or ChadOx-1

BackgroundAlthough important information concerning COVID-19 vaccination is available, the effects of the CoronaVac and ChadOx-1 vaccines on immunity and the redox balance in the upper airway mucosa of the aged population are not fully understood. Therefore, the aim of this study was to investigate the impacts of two doses of the CoronaVac or ChadOx-1 vaccine on immune/inflammatory responses and oxidative stress in the airway mucosa of older adults.MethodsSeventy-six older adults of both sexes, with a mean age of 75.1 ± 6.4 years, were separated according to vaccination status into the CoronaVac (n = 52) and ChadOx-1 (n = 24) groups. Saliva samples were collected before (pre) and 30 days after (post) the administration of the second dose of the CoronaVac or ChadOx-1 vaccine to assess the levels of antibodies (sIgA and IgG), antimicrobial peptides, cytokines, and oxidant/antioxidant agents.ResultsThe immunogenicity in the ChadOx-1 group was 37.5% for sIgA and 25% for IgG, while that in the CoronaVac group was 18.9% for sIgA and 13.2% for IgG. Intergroup analysis revealed that (1) lower levels of IFN-α, IFN-γ, and IL-10 and a greater IFN-γ/IL-10 ratio, in addition to a greater IL-6/IL-10 ratio, were found in both the pre- and postvaccination periods, and (2) lower levels of total sIgA, IL-12p70, IL-17A, TNF-α, and the IL-12p70/IL-10 ratio, in addition to higher levels of specific sIgA for SARS-CoV-2 antigens and lysozyme, were observed only in the postvaccination period in the ChadOx-1 group than in the CoronaVac group. Intragroup analysis revealed (1) a significant increase in the salivary levels of total peroxides in the postvaccination period compared to those in the prevaccination period in both volunteer groups; (2) a decrease in the levels of lysozyme and the ratio between total antioxidant capacity (TAC) and total peroxides in the postvaccination period in the CoronaVac group compared with those in the prevaccination period; and (3) decreases in the TNF-α, IL-6, and IL-12p70 levels, and the IL-12p70/IL-10 ratio in the ChadoX-1 group, as well as a higher lactoferrin concentration in the postvaccination period than in the prevaccination period. Several positive and negative correlations between the parameters assessed here were found.ConclusionsIn general, the ChadOx-1 group exhibited improvements in both immune/inflammatory responses and redox balance and greater immunogenicity than did the CoronaVac group.

Asymptomatic carriage of Plasmodium falciparum in children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio

BackgroundAsymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of different Plasmodium species. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage of Plasmodium falciparum in a highly exposed population.Methods142 asymptomatic Plasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5 ℃) were followed weekly for 10 weeks before being treated with artemisinin-based combination therapy (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. The Plasmodium antigen tested included P. falciparum merozoite extract (ME) and schizont extract (SE), and the recombinant proteins erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119).ResultsMedian levels of IgG against P. falciparum EBA-175 and MSP-119 at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF and MCP-1 levels. A balanced IL-10:TNF ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger.ConclusionThe above findings indicate that asymptomatic carriage of P. falciparum in children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.

Development and validation of machine learning-based prediction model for severe pneumonia: A multicenter cohort study

Severe pneumonia (SP) is a prevalent respiratory ailment characterized by high mortality and poor prognosis. Current scoring systems for pneumonia are not only time-consuming but also exhibit limitations in early SP prediction. To address this gap, this study aimed to develop a machine-learning model using inflammatory markers from peripheral blood for early prediction of SP. A total of 204 pneumonia patients from seven medical centers were studied, with 143 (68 SP cases) in the training cohort and 61 (32 SP cases) in the test cohort. Clinical characteristics and laboratory test results were collected at diagnosis. Various models including Logistic Regression, Random Forest, Naïve Bayes, XGBoost, Support Vector Machine, and Decision Tree were built and evaluated. Seven predictors—age, sex, WBC count, T-lymphocyte count, NLR, CRP, TNF-α, IL-4/IFN-γ ratio, IL-6/IL-10 ratio—were selected through LASSO regression and clinical insight. The XGBoost model, exhibiting best performance, achieved an AUC of 0.901 (95 % CI: 0.827 to 0.985) in the test cohort, with an accuracy of 0.803, sensitivity of 0.844, specificity of 0.759, and F1_score of 0.818. Indeed, SHAP analysis emphasized the significance of elevated WBC counts, older age, and elevated CRP as the top predictors. The use of inflammatory biomarkers in this concise predictive model shows significant potential for the rapid assessment of SP risk, thereby facilitating timely preventive interventions.

O70 INVOLVEMENT OF MICRORNAs-146a-5P, -155-5P, AND -29b-5P IN CARDIAC REMODELLING AND DYSFUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

Background: MicroRNAs have been implicated in the pathogenesis of cardiovascular disease. However, the contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology. Aim: We investigated the role of miR-146a-5p, -155-5p, and -29b-5p in the development of cardiac hypertrophy and dysfunction in male and female spontaneously hypertensive rats (SHR). Methods: Seven (7)-month-old SHR (n=7 male, n=10 female), and age- and sex-matched normotensive Wistar Kyoto rats (WKY, n=7 male, n=9 female) were used for the study. Cardiac geometry and function were determined from echocardiography. Plasma levels of inflammatory markers were measured by ELISA. Collagen fraction area was determined from histological sections of the left ventricle (LV). MicroRNA, and mRNA expression of target genes was determined in the LV by RT-qPCR. Group differences were ascertained from 2-way ANOVA. Associations were determined from pearson's correlation. Results: In SHR, normalised heart and LV masses, LVPWTd, RWT, E, A, E/e’, and collagen fraction area were significantly greater compared to WKY. MidFS, e’, and a’ were significantly lower in SHR versus WKY. Female rats exhibited significantly greater LV mRNA expression of Lox1, Col1a/Col3a ratio, and plasma levels of CRP, IL-6, and TNF-α compared to males. MiR-29b-5p showed similar expression levels across experimental groups. MiR-146a-5p was upregulated in SHR and exhibited positive associations with BP, normalised heart and LV masses, RWT, collagen fraction area, and E/e’ ratio, but negative associations with e’. Conversely, miR-155-5p was downregulated in females and only positively associated with absolute heart, LV, kidney masses, and stroke volume. Conclusion: Upregulation of miR-146a-5p was associated with indices of concentric LVH, diastolic dysfunction, reactive fibrosis, and may be involved in the hypertensive-induced LV remodelling; whereas, changes in expression of miR-155-5p may be involved with a cardiac phenotype related to sexual dimorphism.

Anti-inflammatory Effect of Novel 2-Phenylphthalazin-2-ium Bromides on LPS-induced RAW264.7 Cells and their Mechanism

Background: Inspired by natural anti-inflammatory quaternary benzo[C]phenanthridine alkaloids, novel 2-phenylphthalazin-2-ium bromides were previously designed and synthesized. Objective: The anti-inflammatory effect of 2-phenylphthalazin-2-ium bromides was evaluated based on inflammatory cytokines, and their possible mechanism was explored through the NF-κB, TLR4 and MAPK signaling pathways. Methods: The tested concentrations of two compounds were assessed using MTT assay in vitro. Griess assay was used to determine the changes in nitric oxide (NO) in the cell culture supernatant. qRT‒PCR was used to detect the mRNA levels of inflammatory cytokines, such as IL-6, IL-1ß, IL-10, TNF-α, TLR4 and iNOS. The secretion levels of TNF-α and IL-1β were detected by ELISA. Western blot test was used to detect the protein expression of IL-6, IL-10, TLR4, iNOS, NF-κB, p-P38/P38, p- ERK/ERK and p-JNK/JNK. Results: 2-(3,5-Dichlorophenyl)phthalazin-2-ium bromide (2) with a concentration below 1 μg/mL showed no significant effect on the growth inhibition of RAW264.7 cells, so the concentrations of compound 2 used for experiments were set to 0, 0.25, 0.5 and 1 μg/mL. Compared with the blank control group, the model group showed increased release of NO, transcription levels of IL-6, IL-1ß, IL-10, TNF-α, TLR4 and iNOS (p&lt; 0.05), and ratios of p-P38/P38, p-ERK/ERK, p-JNK/JNK (p&lt; 0.05). Compared with the model group, the sample groups displayed decreased NO release and reduced transcriptional levels of IL-6, IL-1ß, IL-10, TNF-α, TLR4, and iNOS and reduced protein expression ratios of IL-6, IL-1ß, IL-10, TNF-α, NF-κB, TLR4, iNOS, p-P38/P38, p-ERK/ERK and p- JNK/JNK (p&lt; 0.05). Conclusion: This study showed that 2-phenylphthalazin-2-ium bromides partially protected macrophages from the LPS-induced inflammatory response by suppressing TLR4-NF-κB/MAPK signaling and reducing NO production.

Role of circulating microparticles and cytokines in periodontitis associated with diabetes.

Periodontitis is a chronic inflammatory condition that affects the supporting tissues of the teeth, and can lead to serious complications such as tooth loss and systemic health problems, including diabetes, which have a bidirectional relationship with periodontitis. Circulating microparticles originate from different cell types after stimuli such as activation or apoptosis. Interleukins are related to processes in the regulation of the immune response, inflammation, and cell growth. This study aimed to evaluate circulating microparticles as well as interleukins in the plasma, at baseline and 1 month after the end of the non-surgical periodontal treatment. Samples were collected from 45 patients, with moderate to severe periodontitis with diabetes (N = 25) and without diabetes (N = 20). Microparticles were evaluated in the platelet-poor plasma by flow cytometer. Cytokine levels were evaluated by the enzyme immunoabsorption assay (ELISA). Higher levels of the pro-inflammatory cytokines were found in the group with diabetes compared to the non-diabetic group both at baseline and 1 month after the end of the treatment. A higher IL-6/IL-10 ratio was found in patients with diabetes compared to the group without diabetes at T0 and T1, whereas an increased IFN-γ/IL-10 ratio was only found at T1 in patients with diabetes in comparison to the group without diabetes. In the group with diabetes, it was verified positive correlations between IL-10 and IL-6 or IFN-γ and a negative correlation between IL-6 and PMP, at T0; in contrast, in the T1, negative correlations were found between TNF-α and IL-10 or PMP. Besides, at T0, it was evidenced positive correlations both between circulating TNF-α and IL-6, and IL-10 and EMP, as well as a negative correlation between IL-10 and PMP in the group with diabetes. In addition, it was observed in T1 positive correlations between levels of TNF-α and IL-6, IFN-γ, or IL-10, and between PMP and IFN-γ, and between EMP and IL-6, TNF-α and IFN-γ in this group. The results suggest a modulatory effect of the periodontitis associated with diabetes, as well as the periodontal treatment, in the systemic inflammatory status of the participants of the study.

Beneficial Bacteria in the Gut Microbiota May Lead to Improved Metabolic and Immunological Status in Chronic Obstructive Pulmonary Disease.

We included 16 stable COPD patients and 16 healthy volunteer CTLs. The relative abundances of Bifidobacterium spp. (Bf) and Akkermansia muciniphila (Akk) bacteria and the Bacteroidetes and Firmicutes phyla were assessed by qPCR. Pulmonary function was evaluated by spirometry, biochemical parameters by colorimetric methods and plasma cytokine levels by cytometric bead array analysis. The Firmicutes/Bacteroides ratio was related to emergency hospital visits and six-minute walk test (6MWT) results. Furthermore, the relative abundance of Bf was associated with plasma concentrations of glucose, triglycerides, HDL-C and IL-10. In addition, Firmicutes levels and the Firmicutes/Bacteroidetes ratio were associated with the IL-12/IL-10 ratio, while Akk abundance was linked to IL-12 levels. The present findings suggest that the abundance of beneficial bacteria in the GM could influence clinical presentation and immunoregulation in COPD.

Inflammatory response after prehospital high-dose glucocorticoid to patients resuscitated from out-of-hospital cardiac arrest: A sub-study of the STEROHCA trial

BackgroundThe post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized “STERoid for OHCA” (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim of this predefined sub-study was to assess the inflammatory response the first three days of admission. MethodsThe STEROHCA trial enrolled 137 OHCA patients randomized to either a single prehospital injection of methylprednisolone 250 mg or placebo. Inflammatory markers, including pro- and anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, and 72 h post-admission. Mixed-model analyses were applied using log-transformed data to assess group differences. ResultsThe 137 patients included in this sub-study had a median age of 67 years (57 to 74), and the 180-day survival rates were 75% (n = 51/68) and 64% (n = 44/69) in the glucocorticoid and placebo group, respectively. A total of 130 (95%) patients had at least one plasma sample available. The anti-inflammatory cytokine IL-10 was increased at hospital admission in the glucocorticoid group (ratio 2.74 (1.49–5.05), p = 0.006), but the intervention showed the strongest effect after 24 h, decreasing pro-inflammatory levels of IL-6 (ratio 0.06 (0.03–0.10), p < 0.001), IL-8 (ratio 0.53 (0.38–0.75), p < 0.001), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13–0.31), p < 0.001), macrophage inflammatory protein-1-beta (MIP-1b, ratio 0.28 (0.18–0.45), p < 0.001), and tumor necrosis factor-α (TNF-α, ratio 0.6 (0.4–0.8), p = 0.01). ConclusionAdministering high-dose glucocorticoid treatment promptly after resuscitation from OHCA influenced the inflammatory response with a reduction in several systemic proinflammatory cytokines after 24 h. Trial registrationEudraCT number: 2020–000855-11; submitted March 30, 2020.URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04624776.

Conventional and Novel Inflammatory Biomarkers in Chronic Heart Failure Patients with Atrial Fibrillation.

(1) Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity and mortality both in the general population and heart failure patients. Inflammation may promote the initiation, maintenance and perpetuation of AF, but the impact of inflammatory molecular signaling on the association between AF and heart failure remains elusive. (2) Materials and Methods: In 111 patients with chronic stable heart failure, baseline values of conventional (IL-6 and hsCRP) and selected novel inflammatory biomarkers (IL-10, IL-6/IL-10 ratio, orosomucoid and endocan) were determined. Inflammatory biomarkers were compared with respect to the presenting cardiac rhythm. (3) Results: Patients aged below 75 years with AF had significantly higher values of IL-6 and IL-6/IL-10 ratio; IL-6 levels were a significant predictor of AF in both univariate (OR 1.175; 95%CI 1.013-1.363; p = 0.034) and multivariate logistic regression analysis when accounting for other inflammatory biomarkers (OR 1.327; 95% CI 1.068-1.650; p = 0.011). Conversely, there was no association between other novel inflammatory biomarkers and AF. (4) Conclusions: IL-6 levels and the IL-6/IL-10 ratio are associated with AF in patients with chronic stable heart failure under the age of 75 years, suggesting that inflammatory molecular signaling may play a role in the development of AF in the heart failure population.

Primary diffuse large B-cell lymphoma of the central nervous system identified with CSF biomarkers

BackgroundDiagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy.Case presentations.The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3.ConclusionsTaken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.

The relationship of IL-1β/IL-10 ratio, pain degree and CTX-II levels with histopathological features of facet joint osteoarthritis in patients with lumbal spinal canal stenosis

Introduction: Osteoarthritis of the facet joint is the final stage of spinal degeneration. Cytokines are believed to play a crucial role in degenerative joint diseases. This study was conducted to prove the relationship between the IL-1β/IL-10 ratio, the degree of pain, and the levels of CTX-II with the histopathological features of facet joint osteoarthritis in patients with lumbar spinal canal stenosis. Methods: The research design is a Cross-Sectional design with consecutive sampling. This study involves patients diagnosed with lumbar spinal canal stenosis according to the hospital's standard operating procedure from January 2023 to September 2023. CTX-II and Plasma IL-10 cytokine levels were examined using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Histopathology is obtained through staining under a microscope. The data obtained in the study were analyzed, and significant result was p&lt;0.05. Results: A total of 38 samples were obtained. There were more males than females, with 52.6% and 47.4%, respectively. The demographic data showed an average age of 58 years. A statistically significant relationship was found between CTX-II and the histological degree of OA in facet joints, with a p-value of 0.043 (p &lt; 0.05) and a weak positive correlation strength (0.330). Meanwhile, the IL-1β/IL-10 ratio showed a weak positive correlation (0.490) with a p-value of 0.002. ODI exhibited a positive correlation with a strength of (0.393) and a p-value of 0.015. A statistically significant relationship was found for IL-1β with a p-value of 0.039, and IL-10 with a p-value of 0.031 (p &gt; 0.05). The correlation strengths were positive for IL-1β (0.327) and negative for IL-10 (-0.336). Conclusion: There was a relationship between the IL-1β/IL-10 ratio, the degree of pain, and the levels of CTX-II with the histopathological features of facet joint osteoarthritis in patients with lumbar spinal canal stenosis.

Advanced diagnostic approaches for SHAPU: Metagenomic sequencing and interleukin analysis

PurposeSeasonal Hyperacute Panuveitis (SHAPU) is an ocular emergency where the genesis between infective and immunological is under investigation. This is the first report in the literature that attempts to explore the unidentified cause using next-generation metagenomic sequencing and immunomarker analysis. DesignCross-sectional quantitative study. MethodsIn this study, vitreous samples were collected from the SHAPU cases during the outbreak of 2019/2020. The vitreous samples of 10 random cases got selected for metagenomic next-generation sequencing. And 5 vitreous samples ran for immune analysis of levels of interleukin (IL) 6 and 10 using the ELISA technique. The ocular samples were extracted and sequenced on Illumina iSeq100 and analyzed through CZ ID platform. The true hits, for the suspected causative organisms were confirmed using qPCR through designed primers specific for that particular organism. ResultsA total of 30 eyes of 30 patients were included. Upon sequencing the DNA libraries, hits were observed for Streptococcus pneumoniae in 2/10 cases, confirmed by qPCR. IL-6 level was increased in 5/5 cases with IL-6/IL-10 greater than 1. ConclusionWe report the presence of S. pneumoniae for the first time using a metagenomics analysis and increased IL-6 to IL-10 ratio via immune-analysis, indicating that SHAPU could have both infective and immunological facets on its causation.

Bovine colostrum supplementation as a new perspective in depression and substance use disorder treatment: a randomized placebo-controlled study.

This randomized, placebo-controlled, double-blind, parallel study aimed to evaluate the effect of 3-month supplementation of bovine colostrum (BOV-COL; 8x400 mg per day) on the outcomes of depression treatment in hospitalized patients with substance use disorder (SUD). The hypothesis is that BOV-COL supplementation as an add-on treatment results in favorable alternations in selected blood inflammatory markers or neurotransmitters, leading to better depression treatment outcomes compared with placebo (PLA). Patients with a Minnesota Multiphasic Personality Inventory-2 score ≥60 points were enrolled. Twenty-nine participants (n=18 in the BOV-COL group and n=11 in the PLA group) completed the protocol. The mean Beck Depression Inventory-II score was significantly reduced after supplementation in both groups. However, the mean 17-point Hamilton Depression Rating Scale score was decreased in the BOV-COL group, but not in the PLA group. In the BOV-COL group, there was a reduction in interleukin (IL)-1, IL-6, IL-10, the IL-6:IL-10 ratio, IL-17, and tumor necrosis factor alpha (TNF-α), while in the PLA group only IL-6 decreased. Favorable alternations in the total count and differentials of white blood cell subsets were more pronounced in the BOV-COL. There were no changes in neurotransmitter concentrations. BOV-COL supplementation is a promising add-on therapy in patients with depression and SUD.

IL-1 and TNF mediates IL-6 signaling at the maternal-fetal interface during intrauterine inflammation.

IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP). Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation. IUI induced a robust expression of IL6 mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of IL6 mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, ADAM17 (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and IL6R mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced IL6 mRNAs in the AMC and variably decreased elements of IL6 trans-signaling. These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.

Exploring the diagnostic potential of cerebrospinal fluid (CSF) IL-10:IL-6 ratio in patients with primary central nervous system lymphoma (PCNSL).

e14041 Background: Primary Central Nervous System Lymphomas (PCNSL) present significant diagnostic challenges due to their aggressive nature. Current diagnostic methods include neuroimaging, CSF cytology, FDG-PET scans, and biopsies. Building upon the success of the IL-10:IL-6 ratio as a diagnostic biomarker in intraocular lymphoma, this study investigates its potential in PCNSL diagnosis. CSF IL-10:IL-6 ratio emerges as a promising, easily accessible biomarker for early PCNSL detection. Methods: Fifteen histopathologically confirmed PCNSL patients were compared with fifteen CNS inflammatory condition patients and ten patients with other CNS malignancies. Detailed clinical assessments were conducted, and IL-10:IL-6 levels were measured in serum and CSF using Flow cytometry. Results: The CSF IL-10:IL-6 Ratio was elevated (&gt; 1) compared to serum levels in PCNSL patients in contrast to other control groups. The mean age ± SD of PCNSL patients was 55.47 ± 17.29, with a male-to-female ratio of 8:7. The mean (SD) for CSF IL-10:IL-6 ratio in PCNSL was 3.35 (3.88), while the mean (SD) for serum IL-10:IL-6 ratio was 0.438 (1.54). The statistical analysis revealed a significant difference (P = 0.0058 &lt; 0.05). Conversely, comparing the CSF IL-10:IL-6 ratio with serum levels in controls with CNS inflammatory conditions and CNS malignancies showed no statistical significance (P &gt; 0.05). Conclusions: Elevated CSF IL-10 and CSF IL-10/IL-6 ratios suggest their potential as early diagnostic markers for large B cell PCNSL. The IL-10:IL-6 ratio holds promise as a novel, easily accessible biomarker in readily available body fluids for PCNSL diagnosis.

High-intensity interval training mitigates the progression of periodontitis and improves behavioural aspects in rats.

To investigate the effects of high-intensity interval training (HIIT) on periodontitis (PD) progression and behavioural outcomes. Forty-eight Wistar rats were divided into four groups: non-trained (NT); non-trained with PD; HIIT with PD; and HIIT. The HIIT protocol, involving daily treadmill sessions, spanned 8 weeks, with PD induced by ligature after the 6th week. Behavioural tests were conducted to assess anxiety and memory. Post euthanasia, we evaluated the systemic inflammatory profile and oxidative stress markers in the hippocampus and amygdala. A morphological evaluation and elemental composition analysis of the mandibular alveolar bone were performed. PD exacerbated alveolar bone level, bone surface damage and alterations in calcium and phosphorus percentages on the bone surface (p < .05), while HIIT attenuated these changes (p < .05). HIIT improved systemic inflammatory markers altered by PD (tumour necrosis factor [TNF]-α, interleukin [IL]-10, TNF-α/IL-10 and IL-1β/IL-10 ratios, p < .05). PD animals exhibited lower total antioxidant capacity and levels of thiobarbituric acid reactive substances in the amygdala and hippocampus, respectively (p < .05). HIIT maintained these parameters at levels similar to those in NT animals. HIIT improved anxiety and memory outcomes altered by PD (p < .05). HIIT attenuates systemic inflammation, anxiety and memory outcomes promoted by PD.

Pap12-6: A host defense peptide with potent immunomodulatory activity in a chicken hepatic cell culture.

In the fight against antimicrobial resistance, host defense peptides (HDPs) are increasingly referred to as promising molecules for the design of new antimicrobial agents. In terms of their future clinical use, particularly small, synthetic HDPs offer several advantages, based on which their application as feed additives has aroused great interest in the poultry sector. However, given their complex mechanism of action and the limited data about the cellular effects in production animals, their investigation is of great importance in these species. The present study aimed to examine the immunomodulatory activity of the synthetic HDP Pap12-6 (PAP) solely and in inflammatory environments evoked by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (Poly I:C), in a primary chicken hepatocyte-non-parenchymal cell co-culture. Based on the investigation of the extracellular lactate dehydrogenase (LDH) activity, PAP seemed to exert no cytotoxicity on hepatic cells, suggesting its safe application. Moreover, PAP was able to influence the immune response, reflected by the decreased production of interleukin (IL)-6, IL-8, and "regulated on activation, normal T cell expressed and secreted"(RANTES), as well as the reduced IL-6/IL-10 ratio in Poly I:C-induced inflammation. PAP also diminished the levels of extracellular H2O2 and nuclear factor erythroid 2-related factor 2 (Nrf2) when applied together with Poly I:C and in both inflammatory conditions, respectively. Consequently, PAP appeared to display potent immunomodulatory activity, preferring to act towards the cellular anti-inflammatory and antioxidant processes. These findings confirm that PAP might be a promising alternative for designing novel antimicrobial immunomodulatory agents for chickens, thereby contributing to the reduction of the use of conventional antibiotics.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.