Plasma IL-6 Research Articles

Mediators of monocyte chemotaxis and matrix remodeling are associated with mortality and pulmonary fibroproliferation in patients with severe COVID-19.

Acute respiratory distress syndrome (ARDS) has a fibroproliferative phase that may be followed by pulmonary fibrosis. Pulmonary fibrosis following COVID-19 pneumonia has been described at autopsy and following lung transplantation. We hypothesized that protein mediators of tissue remodeling and monocyte chemotaxis are elevated in the plasma and endotracheal aspirates of critically ill patients with COVID-19 who subsequently develop features of pulmonary fibroproliferation. We enrolled COVID-19 patients admitted to the ICU with hypoxemic respiratory failure. (n = 195). Plasma was collected within 24h of ICU admission and at 7d. In mechanically ventilated patients, endotracheal aspirates (ETA) were collected. Protein concentrations were measured by immunoassay. We tested for associations between protein concentrations and respiratory outcomes using logistic regression adjusting for age, sex, treatment with steroids, and APACHE III score. In a subset of patients who had CT scans during hospitalization (n = 75), we tested for associations between protein concentrations and radiographic features of fibroproliferation. Among the entire cohort, plasma IL-6, TNF-α, CCL2, and Amphiregulin levels were significantly associated with in-hospital mortality. In addition, higher plasma concentrations of CCL2, IL-6, TNF-α, Amphiregulin, and CXCL12 were associated with fewer ventilator-free days. We identified 20/75 patients (26%) with features of fibroproliferation. Within 24h of ICU admission, no measured plasma proteins were associated with a fibroproliferative response. However, when measured 96h-128h after admission, Amphiregulin was elevated in those that developed fibroproliferation. ETAs were not correlated with plasma measurements and did not show any association with mortality, ventilator-free days (VFDs), or fibroproliferative response. This cohort study identifies proteins of tissue remodeling and monocyte recruitment are associated with in-hospital mortality, fewer VFDs, and radiographic fibroproliferative response. Measuring changes in these proteins over time may allow for early identification of patients with severe COVID-19 at risk for fibroproliferation.

Relationship between Respiratory Microbiome and Systemic Inflammatory Markers in COPD: A Pilot Study.

The respiratory microbiome may influence the development and progression of COPD by modulating local immune and inflammatory events. We aimed to investigate whether relative changes in respiratory bacterial abundance are also associated with systemic inflammation, and explore their relationship with the main clinical COPD phenotypes. Multiplex analysis of inflammatory markers and transcript eosinophil-related markers were analyzed on peripheral blood in a cohort of stable COPD patients (n = 72). Respiratory microbiome composition was analyzed by 16S rRNA microbial sequencing on spontaneous sputum. Spearman correlations were applied to test the relationship between the microbiome composition and systemic inflammation. The concentration of the plasma IL-8 showed an inverted correlation with the relative abundance of 17 bacterial genera in the whole COPD cohort. COPD patients categorized as eosinophilic showed positive relationships with blood eosinophil markers and inversely correlated with the degree of airway obstruction and the number of exacerbations during the previous year. COPD patients categorized as frequent exacerbators were enriched with the bacterial genera Pseudomonas which, in turn, was positively associated with the severity of airflow limitation and the prior year's exacerbation history. The associative relationships of the sputum microbiome with the severity of the disease emphasize the relevance of the interaction between the respiratory microbiota and systemic inflammation.

Therapeutic potential of cannabis for surgical wound healing in rats.

This study was conducted to evaluate the wound-healing activities of a Cannabis sativa L. plant extract and cannabidiol on incision wounds. An incision was created and sutured in rats under anaesthesia. Routine wound care procedures were applied for 10 days, followed by histological wound examinations. The cellular bioactivities of the hemp extract and CBD were assessed for MCP-1, EGF, BFGF, IL-8, and COL-1 using ELISA on the rat skin wound healing activity. A one-way ANOVA was used for the data analysis. The EGF values in the plasma were similar in the povidone-iodine, hemp seed oil, and hemp essential oil groups (P > 0.05). However, the EGF levels were lower in the CBD group compared to the other groups (P < 0.001, P < 0.005). The MCP-1 values in the hemp seed oil, hemp essential oil, and CBD were similar (P > 0.05), whereas povidone iodine exhibited lower MCP-1 levels compared to the other groups (P < 0.001, P < 0.005). It was determined that the plasma BFGF, IL-8, and COL 1 values of the groups were similar (P > 0.05). To our knowledge, this study is the first to evaluate the effects of CBD, seed oil, and hemp leaf extract on incision wound healing. It demonstrates that hemp extract holds greater potential benefits for wound healing compared to CBD.

Analysis of 12 kinds of cytokines in seminal plasma by flow cytometry and their correlations with routine semen parameters

ObjectiveTo investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. MethodsThe remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. ResultsThe r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1β and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). ConclusionThere are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.

Comparative Study of Blood Neopterin and Biopterins in Patients with COVID-19 and Secondary Bacterial Infection.

Background/Objectives: As COVID-19 can be severe, early predictive markers of both severity and onset of secondary bacterial infections are needed. This study first examined changes over time in the levels of plasma neopterin (NP) and biopterins (BPs), among others, in patients with COVID-19 and then in those with secondary bacterial infection complications. Methods: Fifty-two patients with COVID-19 admitted to two tertiary care centers were included. They were divided into a severe group (intubated + mechanical ventilation) (n = 10) and a moderate group (non-intubated + oxygen administration) (n = 42), and changes over time in plasma NP, plasma BPs, IFN-γ, lymphocyte count, CRP, and IL-6 were investigated. Four of the patients in the severe group (n = 10) developed secondary bacterial infections during treatment. Plasma NP and plasma BPs of patients with bacterial sepsis (no viral infection) (n = 25) were also examined. Results: The plasma NP, IL-6, CRP, and SOFA levels were significantly higher in the severe group, while the IFN-γ level and lymphocyte count were significantly lower. The higher plasma NP in the severe group persisted only up to 1 week after symptom onset. The plasma BPs were higher in complications of bacterial infection. Conclusions: The timing of sample collection is important for assessing severity through plasma NP, while plasma BPs may be a useful diagnostic tool for identifying the development of secondary bacterial infection in patients with COVID-19. Further investigation is needed to clarify the mechanism by which NP and BPs, which are involved in the same biosynthetic pathway, are differentially activated depending on the type of pathogen.

Phase I study of the safety and clinical activity of the interleukin-8 inhibitor AMY109 combined with atezolizumab in patients with advanced solid cancers

BackgroundImmunosuppressive conditions within the tumor microenvironment (TME) can allow tumors to evade the immune system, including by hampering programmed death ligand 1 (PD-L1) inhibitor activity. Interleukin (IL)-8 contributes to immunosuppression...

Immune response and cytokine profiles in post-laminectomy pain syndrome: comparative analysis after treatment with intrathecal opioids, oral opioids, and non-opioid therapies.

This study explores the interaction between cytokines, cell-mediated immunity (T cells, B cells, and NK cells), and prolonged morphine administration in chronic neuropathic pain patients without cancer-related issues. Despite evidence of opioid immunomodulation, few studies have compared these interactions. In a cross-sectional and comparative study, 50 patients with chronic low back radicular pain ("Failed Back Surgery Syndrome") were categorized into intrathecal morphine infusion (IT group, n = 18), oral morphine (PO group, n = 17), and non-opioid treatment (NO group, n = 15). Various parameters, including plasma and cerebrospinal fluid (CSF) cytokine concentrations, lymphocyte immunophenotyping, opioid escalation indices, cumulative morphine dose, and treatment duration, were assessed. CSF IL-8 and IL-1β concentrations exceeded plasma levels in all patients. No differences in T, B, and NK lymphocyte numbers were observed between morphine-treated and non-treated patients. Higher plasma IL-5 and GM-CSF concentrations were noted in IT and PO groups compared to NO. CSF IFNγ concentrations were higher in PO and NO than IT. Positive correlations included CD4 concentrations with opioid escalation indices, and negative correlations involved NK cell concentrations, CSF TNFα concentrations, and opioid escalation indices. Positive correlations were identified between certain cytokines and pain intensity in IT patients, and between NK cells and cumulative morphine dose. Negative correlations were observed between CSF IL-5 concentrations and pain intensity in IT and PO, and between opioid escalation indices and CSF cytokine concentrations in PO and IT. Associations between cytokines, cellular immunity, and prolonged morphine treatment, administered orally and intrathecally were identified.

Racial Disparities in Plasma Cytokine and Microbiome Profiles.

Many health issues prevalent in African American (AA) populations are associated with chronic inflammation and related health conditions, including autoimmune diseases, infectious diseases, neurologic disorders, metabolic syndromes, and others. The current study aims to understand plasma microbiome translocation as a potential trigger for chronic inflammation. In this study, 16 Caucasian American (CA) and 22 African American (AA) healthy individuals were recruited. Microbial DNA was isolated from the plasma samples and sequenced via microbial 16S rRNA V3-4 sequencing. The plasma levels of 33 cytokines and chemokines were evaluated. The proinflammatory microbiomes were verified using human THP-1 cells in vitro. The plasma levels of IL-6, IL-15, MIP-1α, MIP-1β, and MIP-3α were higher in the AA people, whereas IL-1α and IL-27 were elevated in the CA people. The plasma microbiomes exhibited eight bacterial genera/phyla differentially enriched in the CA and AA people. Given the critical role of IL-6 in chronic inflammation and associated diseases, we identified five bacteria genera significantly associated with IL-6. The abundance of Actinomyces was positively correlated with the plasma IL-6 level (r = 0.41, p = 0.01), while the abundance of Kurthia (r = -0.34, p = 0.04), Noviherbaspirillum (r = -0.34, p = 0.04), Candidatus Protochlamydia (r = -0.36, p = 0.03), and Reyranella (r = -0.39, p = 0.02) was negatively correlated with this. Finally, the THP-1 cells treated with heat-killed bacteria produced higher levels of IL-6 in vitro in response to the Actinomyces species compared to the species in the genus either uncorrelated or negatively correlated with IL-6. This is the first study to report potential blood microbiome translocation as a driver for persistently elevated IL-6 levels in the periphery in healthy AA versus CA people. Understanding the plasma microbiome linked to the IL-6 levels in people with different racial backgrounds is essential to unraveling the therapeutic approaches to improve precision medicine.

Comparative evaluation of the effectiveness of balneotherapy and balneotherapy in combination with intravenous laser irradiation of blood at the period of spa treatment of patients with psoriasis

Background. Psoriasis is one of the most common, chronic, recurrent dermatoses. To date, a sufficient pool of studies has been accumulated confirming the multifactorial genesis of psoriasis due to genetic and environmental factors. Aim. Сomparative assessment of the effect of different options for spa treatment (ST) balneotherapy and balneotherapy in combination with intravenous laser blood irradiation (ILBI) in patients with psoriasis vulgaris on the level of IL-6 and IL-17, dermatological and psycho-emotional status, assessment of quality of life. Methods. The comparative study involved 108 patients with psoriasis vulgaris, stationary stage (men — 57.4%, women — 42.6%; the average age was 36.2 [24.5; 47.9] years) who underwent spa treatment, which were subsequently divided into 2 groups: 52 patients who received balneotherapy along with the traditional complex of ST were included in the 1 group, 56 patients who received complex treatment were included in the 2 group. The effectiveness of ST was evaluated using the PASI index, the HARS and HDRS scale, the SF-36 questionnaire. The dynamics of IL-6 and IL-10 levels in blood plasma were evaluated. The total duration of the study was 6 months and 14 days: the treatment phase was 14 days and the follow-up phase was 3 and 6 months after the completion of ST. Results. After 14 days of ST in the group in which balneotherapy was performed in combination with IVBI, a statistically significant decrease in the PASI index was more pronounced compared to the group in which balneotherapy was performed (p). Balneotherapy did not have a pronounced effect on psychoemotional status. On the contrary, balneotherapy in combination with ILBI contributed to a statistically significant decrease in the final indicators on the HARS and HDRS scales. The decrease in IL-6 and IL-17 levels was statistically significant in both groups and there were no differences between them. The complex use of balneotherapy and ILBI in comparison with the group of balneotherapy was accompanied by a more pronounced improvement in QOL. The combined use of balneotherapy and ILBI in the follow-up phase showed a long-term positive effect: 6 months after the completion of ST, the number of patients who had clinical remission was statistically significantly higher compared to the group in which balneotherapy was performed (87.4 vs. 44.7%). Conclusion. The advantage of the combined use of balneotherapy and ILBI compared with balneotherapy in patients with psoriasis vulgaris on CL was shown. The complex use of balneotherapy and ILBI of significant indicators of inflammatory biomarkers, improvement of the dermatological and psycho-emotional state, quality of life parameters and good overpopulation. More pronounced effectiveness of the complex use of balneotherapy and ILBI compared to balneotherapy of the quality, diversity of pathophysiological mechanisms of psoriasis and the presence of several targets for pathogenetic therapy.

Effects of Aerobic Exercise on Brain Age and Health in Middle-Aged and Older Adults: A Single-Arm Pilot Clinical Trial.

Sleep disturbances are prevalent among elderly individuals. While polysomnography (PSG) serves as the gold standard for sleep monitoring, its extensive setup and data analysis procedures impose significant costs and time constraints, thereby restricting the long-term application within the general public. Our laboratory introduced an innovative biomarker, utilizing artificial intelligence algorithms applied to PSG data to estimate brain age (BA), a metric validated in cohorts with cognitive impairments. Nevertheless, the potential of exercise, which has been a recognized means of enhancing sleep quality in middle-aged and older adults to reduce BA, remains undetermined. We conducted an exploratory study to evaluate whether 12 weeks of moderate-intensity exercise can improve cognitive function, sleep quality, and the brain age index (BAI), a biomarker computed from overnight sleep electroencephalogram (EEG), in physically inactive middle-aged and older adults. Home wearable devices were used to monitor heart rate and overnight sleep EEG over this period. The NIH Toolbox Cognition Battery, in-lab overnight polysomnography, cardiopulmonary exercise testing, and a multiplex cytokines assay were employed to compare pre- and post-exercise brain health, exercise capacity, and plasma proteins. In total, 26 participants completed the initial assessment and exercise program, and 24 completed all procedures. Data are presented as mean [lower 95% CI of mean, upper 95% CI of mean]. Participants significantly increased maximal oxygen consumption (Pre: 21.11 [18.98, 23.23], Post 22.39 [20.09, 24.68], mL/kg/min; effect size: -0.33) and decreased resting heart rate (Pre: 66.66 [63.62, 67.38], Post: 65.13 [64.25, 66.93], bpm; effect size: -0.02) and sleeping heart rate (Pre: 64.55 [61.87, 667.23], Post: 62.93 [60.78, 65.09], bpm; effect size: -0.15). Total cognitive performance (Pre: 111.1 [107.6, 114.6], Post: 115.2 [111.9, 118.5]; effect size: 0.49) was significantly improved. No significant differences were seen in BAI or measures of sleep macro- and micro-architecture. Plasma IL-4 (Pre: 0.24 [0.18, 0.3], Post: 0.33 [0.24, 0.42], pg/mL; effect size: 0.49) was elevated, while IL-8 (Pre: 5.5 [4.45, 6.55], Post: 4.3 [3.66, 5], pg/mL; effect size: -0.57) was reduced. Cognitive function was improved by a 12-week moderate-intensity exercise program in physically inactive middle-aged and older adults, as were aerobic fitness (VO2max) and plasma cytokine profiles. However, we found no measurable effects on sleep architecture or BAI. It remains to be seen whether a study with a larger sample size and more intensive or more prolonged exercise exposure can demonstrate a beneficial effect on sleep quality and brain age.

Effects of altering the ratio of C16:0 and cis-9 C18:1 in rumen bypass fat on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls

BackgroundC16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo. This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls. Thirty finishing Angus bulls (626 ± 69 kg, 21 ± 0.5 months) were divided into 3 treatments according to the randomized block design: (1) control diet without additional fat (CON), (2) CON + 2.5% palmitic acid calcium salt (PA, 90% C16:0), and (3) CON + 2.5% mixed fatty acid calcium salt (MA, 60% C16:0 + 30% cis-9 C18:1). The experiment lasted for 104 d, after which all the bulls were slaughtered and sampled for analysis.ResultsMA tended to reduce 0–52 d dry matter intake compared to PA (DMI, P = 0.052). Compared with CON and MA, PA significantly increased 0–52 d average daily gain (ADG, P = 0.027). PA tended to improve the 0–52 d feed conversion rate compared with CON (FCR, P = 0.088). Both PA and MA had no significant effect on 52–104 days of DMI, ADG and FCR (P > 0.05). PA tended to improve plasma triglycerides compared with MA (P = 0.077), significantly increased plasma cholesterol (P = 0.002) and tended to improve subcutaneous adipose weight (P = 0.066) when compared with CON and MA. Both PA and MA increased visceral adipose weight compared with CON (P = 0.021). Only PA increased the colonization of Rikenellaceae, Ruminococcus and Proteobacteria in the cecum, and MA increased Akkermansia abundance (P < 0.05). Compared with CON, both PA and MA down-regulated the mRNA expression of Claudin-1 in the jejunum (P < 0.001), increased plasma diamine oxidase (DAO, P < 0.001) and lipopolysaccharide (LPS, P = 0.045). Compared with CON and MA, PA down-regulated the ZO-1 in the jejunum (P < 0.001) and increased plasma LPS-binding protein (LBP, P < 0.001). Compared with CON, only PA down-regulated the Occludin in the jejunum (P = 0.013). Compared with CON, PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose (P < 0.001) and increased plasma IL-6 (P < 0.001). Compared with CON, only PA up-regulated the TNF-α in the visceral adipose (P = 0.01). Compared with CON and MA, PA up-regulated IL-6 in the visceral adipose (P < 0.001), increased plasma TNF-α (P < 0.001), and reduced the IgG content in plasma (P = 0.035). Compared with CON, PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle (P < 0.05), while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1. However, neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON (P > 0.05).ConclusionsMA containing 30% cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity, adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization, improving colonization of Akkermansia, reducing intestinal barrier damage, and down-regulating NF-κB activation.

Prolonged premature rupture of membranes with increased risk of infection is associated with gut accumulation of Pseudomonas from the environment

BackgroundPreterm premature rupture of membranes (PPROM) contributes to over one-third of preterm births, and PPROM infants are more susceptible to infections. However, the risk factors remain poorly understood. We here aim to investigate the association of duration of premature rupture of membranes (PROM) and environmental microbiota with the gut microbiota and infection in PPROM infants. MethodsForty-six premature infants were recruited from two hospitals, and infant fecal and environmental samples were collected. 16 s rRNA sequencing was performed to analyze the fecal and environmental microbiome. Human inflammatory cytokines in cord vein plasma were measured. ResultsThe gut microbiota composition of PPROM infants was different from that of non-PPROM infants, and the microbiome phenotypes were predicted to be associated with a higher risk of infection, further evidenced by the significantly increased levels of IL-6 and IL-8 in cord vein plasma of PPROM infants. The diversity of the gut microbiota in PPROM infants increased significantly as the duration of PROM excessed 12 h, and Pseudomonas contributed significantly to the dynamic changes. The Pseudomonas species in the gut of PPROM infants were highly homologous to those detected in the ward environment, suggesting that prolonged PROM is associated with horizontal transmission of environmental pathogens, leading to a higher risk of infection. ConclusionsThis study highlights that the duration of PROM is associated with the accumulation of environmental pathogens in the gut of PPROM infants, which is a risk factor for nosocomial infections. Improving environmental hygiene could be effective in optimizing the clinical care of PPROM infants.

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.

Additive effects of depression and obesity on neural correlates of inhibitory control

BackgroundDepression and obesity are associated with impaired inhibitory control. Behavioral evidence indicates an exacerbating additive effect when both conditions co-occur. However, the underlying neural mechanisms remain unclear. Moreover, systemic inflammation affects neurocognitive performance in both individuals with depression and obesity. Here, we investigate additive effects of depression and obesity on neural correlates of inhibitory control, and examine inflammation as a connecting pathway. MethodsWe assessed inhibitory control processing in 64 individuals with obesity and varying degrees of depressed mood by probing neural activation and connectivity during an fMRI Stroop task. Additionally, we explored associations of altered neural responses with individual differences in systemic inflammation. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study. ResultsConcurrent depression and obesity were linked to increased functional connectivity between the supplementary motor area and precuneus and between the inferior occipital and inferior parietal gyrus. Exploratory analysis revealed that circulating inflammation markers, including plasma leptin, IL-6, IL-8, and CCL-3 correlated with the additive effect of depression and obesity on altered functional connectivity. LimitationsThe observational design limits causal inferences. Future research employing longitudinal or intervention designs is required to validate these findings and elucidate causal pathways. ConclusionThese findings suggest increased neural crosstalk underlying impaired inhibitory control in individuals with concurrent obesity and depressed mood. Our results support a model of an additive detrimental effect of concurrent depression and obesity on neurocognitive functioning, with a possible role of inflammation.

Burkholderia cepacia in cystic fibrosis children and adolescents: overall survival and immune alterations.

In current literature there are only scarce data on the host inflammatory response during Burkholderia cepacia complex (Bcc) persistence. The primary objective of the present research was to carry out cross-sectional analyses of biomarkers and evaluate disease progression in cystic fibrosis (CF) patients with chronic Bcc infection and pathogen-free ones. The secondary aim was to assess prospectively overall survival of the study participants during up to 8 years of follow-up. The study included 116 paediatric patients with CF; 47 CF patients were chronically infected with Bcc, and 69 individuals were Bcc free. Plasma and sputum biomarkers (neutrophil elastase, MMP-8, MMP-9, MMP-12, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-22, IL-23, IL-17, IFN-γ, TGFβ1, TNF-α) were analysed using commercially available kits. Besides, inhibitory effect of dexamethasone on proliferative response of PHA-stimulated peripheral blood lymphocytes had been assessed. Bcc infected patients did not differ from Bcc free ones in demographic and clinical parameters, but demonstrated an increased rate of glucose metabolism disturbances and survival disadvantage during prolong follow-up period. Biomarkers analyses revealed elevated TNF-α and reduced IL-17F levels in sputum samples of Bcc infected patients. These patients also demonstrated improvement of peripheral blood lymphocyte sensitivity to steroid treatment and reduction in plasma pro-inflammatory (IL-17F and IL-18) and anti-inflammatory (TGFβ1 and IL-10) cytokine concentrations. Reduction in IL-17F levels may have several important consequences including increase in steroid sensitivity and glycemic control disturbances. Further investigations are needed to clarify the role of IL-17 cytokines in CF complication development. Low plasma TGFβ1 and IL-10 levels in Bcc infected group may be a sign of subverted activity of regulatory T cells. Such immune alterations may be one of the factors contributing to the development of the cepacia syndrome.

ILC2s induce Treg but not Th2-type immunity through IL-33/ST2 pathway in pulmonary tuberculosis.

We investigated the function of type 2 innate lymphoid cells (ILC2s) and IL-33 in pulmonary tuberculosis (PTB). Peripheral blood samples were collected from PTB patients and healthy controls. The cytometric bead array was used to detect plasma IL-33, TGF-β, IL-4, IL-5, IL-6, IL-10, IL-13, and soluble ST2 (sST2). ILC2s, Th2, and Treg cells were detected with flow cytometry. Quantitative real-time PCR was used to measure mRNA levels. ILC2s were co-cultured with peripheral blood mononuclear cells and then intervened with IL-33 or anti-ST2 antibody + IL-33 in vitro. IL-4, IL-6, IL-5, IL-10, IL-13, and TGF-β levels were measured by enzyme-linked immunosorbent assay. Compared with healthy controls, the levels of IL-33, sST2, TGF-β, IL-10, and IL-6 in the plasma of PTB patients were significantly higher. No significant difference was found in the plasma IL-4, IL-5, and IL-13 levels. Patients with PTB had significantly increased ILC2s proportion and mRNA levels of RAR-related orphan receptor α and GATA binding protein 3. After 48 h of IL-33 stimulation in vitro, Treg cell proportion significantly increased and the IL-10 level was significantly elevated. Treatment with anti-ST2 abolished these effects. No significant difference was found in cytokines of IL-4, IL-6, IL-5, IL-13, and TGF-β, or Th2 cells before and after IL-33 treatment. ILC2s proportion in peripheral blood was increased and plasma IL-33 was upregulated in PTB patients. IL-33 may promote the growth of ILC2s and the production of Treg-related cell cytokines, but not Th2-related cell cytokines, to participate in immune response to PTB.

Non-Surgical Periodontal Therapy's Influence on Alpha-Synuclein and Inflammatory Marker Levels: A Pilot Study.

Background: Microbial dysbiosis may contribute to alpha-synuclein (α-Syn) homeostasis disruption, yet the burden of inflammatory periodontal infection and its treatment have never been studied in this regard. We aimed to compare the cytokine and α-Syn levels in the saliva and blood of patients with periodontitis who underwent non-surgical periodontal therapy (NSPT) and those of their healthy counterparts. Methods: Periodontal examination and saliva and blood sample collection were carried out in incoming patients at a university clinic. The periodontitis group (PG) received NSPT. The sample collection and periodontal observation were repeated 30 days after. IL-6, IL1-β and total α-Syn were quantified using immunoassay methods. The periodontal inflamed surface area (PISA) was calculated as a proxy for periodontal inflammation. Results: Eleven participants formed the PG, and there were fifteen healthy controls (HC). At baseline, no correlation between salivary and plasma α-Syn was found. The salivary α-Syn levels revealed a tendency to decrease 30 days after, particularly in the PD cases. The variation in PISA and α-Syn showed significant correlation. Salivary α-Syn correlated negatively with salivary IL-6 levels at both timepoints in the total sample (rho = -0.394 and rho = -0.451) and in the HC (rho = -0.632 and rho = -0.561). Variations in plasma IL-6 and α-Syn were negatively correlated (rho = -0.518) in the healthy participants. Baseline plasma IL1-β negatively correlated with plasmatic α-Syn at 30 days in the HC (rho = -0.581). Conclusions: Salivary and plasma α-Syn bioavailability operate independently, and periodontal diagnosis was not a confounding factor. Salivary α-Syn levels were significantly affected by NSPT, contrary to plasma levels. These results should be confirmed in future larger and prospective studies.

The synergistic effects of mechanical ventilation and intrauterine inflammation on cerebral inflammation in preterm fetal sheep.

Intrauterine inflammation and the requirement for mechanical ventilation independently increase the risk of perinatal brain injury and adverse neurodevelopmental outcomes. We aimed to investigate the effects of mechanical ventilation for 24 h, with and without prior exposure to intrauterine inflammation, on markers of brain inflammation and injury in the preterm sheep brain. Chronically instrumented fetal sheep at ~115 days of gestation were randomly allocated to receive a single intratracheal dose of 1 mg lipopolysaccharide (LPS) or isovolumetric saline, then further randomly allocated 1 h after to receive mechanical ventilation with room air or no mechanical ventilation (unventilated control + saline [UVC, n = 7]; in utero mechanical ventilation + saline [VENT, n = 8], unventilated control + intratracheal LPS [UVC + LPS, n = 7]; in utero ventilation + intratracheal LPS [VENT + LPS, n = 7]). Serial fetal blood and plasma samples were collected throughout the experimental protocol for assessment of blood biochemistry and plasma interleukin (IL)-6 levels. After 24 h of mechanical ventilation, fetal brains were collected for RT-qPCR and immunohistochemical analyses. LPS exposure increased numbers of microglia and upregulated pro-inflammatory related genes within the cortical gray matter (GM) and subcortical white matter (SCWM) (pLPS < 0.05). Mechanical ventilation alone increased astrocytic cell density in the periventricular white matter (PVWM) (pVENT = 0.03) but had no effect on pro-inflammatory gene expression. The combination of ventilation and LPS increased plasma IL-6 levels (p < 0.02 vs. UVC and VENT groups), and exacerbated expression of pro-inflammatory-related genes (IL1β, TLR4, PTGS2, CXCL10) and microglial density (p < 0.05 vs. VENT). This study demonstrates that 24 h of mechanical ventilation after exposure to intrauterine inflammation increased markers of systemic and brain inflammation and led to the upregulation of pro-inflammatory genes in the white matter. We conclude that 24 h of mechanical ventilation following intrauterine inflammation may precondition the preterm brain toward being more susceptible to inflammation-induced injury.

Exercise4Psychosis: A randomised control trial assessing the effect of moderate-to-vigorous exercise on inflammatory biomarkers and negative symptom profiles in men with first-episode psychosis

IntroductionFirst-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP. MethodsSeventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60–70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise. ResultsParticipants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (−3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (–22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (−13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05). DiscussionRegular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication.

Plasma IL-6 levels and their association with brain health and dementia risk: A population-based cohort study

BackgroundRecent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL-6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts. MethodsThis study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL-6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL-6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels. ResultsA total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23–35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels. ConclusionsIncreased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk.