Changes In Cytokine Levels Research Articles

Proof of Concept: Effects of an Immune-Enhancing Formula on Clinical Markers of Critical Coronavirus Disease 2019 Cases

Background/Objectives: The rapid viral spread observed in coronavirus disease 2019 (COVID-19) is capable of inducing the secretion of excessive inflammatory cytokines. The resulting multi-organ damage is a severe complication that can be attenuated through adequate nutrition. Formulae enhanced with either glutamine or arginine are conditionally essential amino acids that have been proven to improve the condition of hospitalized patients. This retrospective study aimed to investigate the effects of administering an immune-enhancing enteral formula enhanced with arginine and glutamine on the clinical signs and biomarkers of patients with severe COVID-19. Methods: After checking the data of 232 patients enrolled in the biobank for completeness and eligibility, 31 patients with severe COVID-19 in the intensive care unit at Taipei Tzu Chi Hospital were grouped based on the type of enteral formula used: 16 patients received the control formula, and 15 patients received the immune-enhancing formula. Baseline characteristics, clinical signs, and inflammatory markers were analyzed for differences. Results: An increase in IL-10 levels in the intervention group was observed (p = 0.048). Changes in other inflammatory cytokine levels were insignificant. Conclusions: Providing an enteral formula enriched with glutamine and arginine to severe COVID-19 patients may help improve their anti-inflammatory marker levels. Further interventional study utilizing enteral formula enriched with glutamine and arginine is needed to confirm the findings of this study.

The Impact of Maternal Chronic Inflammatory Conditions on Breast Milk Composition: Possible Influence on Offspring Metabolic Programming

Breastfeeding is the best way to provide newborns with crucial nutrients and produce a unique bond between mother and child. Breast milk is rich in nutritious and non-nutritive bioactive components, such as immune cells, cytokines, chemokines, immunoglobulins, hormones, fatty acids, and other constituents. Maternal effects during gestation and lactation can alter these components, influencing offspring outcomes. Chronic inflammatory maternal conditions, such as obesity, diabetes, and hypertension, impact breast milk composition. Breast milk from obese mothers exhibits changes in fat content, cytokine levels, and hormonal concentrations, potentially affecting infant growth and health. Similarly, diabetes alters the composition of breast milk, impacting immune factors and metabolic markers. Other pro-inflammatory conditions, such as dyslipidemia and metabolic syndrome, have been barely studied. Thus, maternal obesity, diabetes, and altered tension parameters have been described as modifying the composition of breast milk in its macronutrients and other important biomolecules, likely affecting the offspring’s weight. This review emphasizes the impact of chronic inflammatory conditions on breast milk composition and its potential implications for offspring development through the revision of full-access original articles.

Changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction complicated with obstructed meibomian gland dysfunction

BackgroundEpiphora and secondary ocular surface damage are increasingly impairing the quality of life of people, particularly elderly women. We aimed to investigate the changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) complicated with obstructed meibomian gland dysfunction (OMGD) and preliminary explore the pathological mechanisms of OMGD in patients with PANDO.MethodsThe prospective study involved 43 and 41 postmenopausal women with and without PANDO, respectively. Based on the presence or absence of OMGD, the participants were subdivided. Tear fluid was collected from affected eyes of all participants using Schirmer I test and tested for cytokine concentrations (interleukin (IL)-6, IL-8, IL-1β, interferon-gamma, tumour necrotic factor (TNF)-α, IL-10, epidermal growth factor (EGF)) using the Multiplex Luminex Assay. Tear lactoferrin levels was determined using ELISA.ResultsIn the PANDO with OMGD group, the IL-8, IL-1α, IL-1β, and macrophage inflammatory protein-1α levels were significantly higher than those in the other groups. The IL-6 and TNF-α levels were significantly higher than those in the controls. The lactoferrin level in the PANDO with OMGD group was lower than that in the Non-PANDO with OMGD group. The IL-10 and EGF levels were not significantly different among the groups.ConclusionThe level of pro-inflammatory factors in the tears of patients with PANDO complicated with OMGD was significantly increased, which is likely to cause further damage to ocular surface. Anti-inflammatory therapy may help protect ocular surface in postmenopausal women with PANDO.

Protective immunity induced by a novel P1 adhesin C-terminal anchored mRNA vaccine against Mycoplasma pneumoniae infection in BALB/c mice.

Mycoplasma pneumoniae (Mp), a unique pathogen devoid of a cell wall, is naturally impervious to penicillin antibiotics. This bacterium is the causative agent of M. pneumoniae pneumonia, an acute pulmonary affliction marked by interstitial lung damage. Non-macrolide medications may have potential adverse effects on the developmental trajectory of children, thereby establishing macrolides as the preferred treatment for M. pneumoniae in pediatric patients. However, the emergence of macrolide-resistant and multidrug-resistant strains of M. pneumoniae presents significant challenges to clinical management and public health. Vaccines, particularly those based on mRNA technology, are regarded as a promising avenue for preventing and controlling M. pneumoniae infections due to their inherent safety, immunogenicity, and adaptability. Our research delves into the P1 adhesin of M. pneumoniae, a protein that binds to host cell receptors with its immunodominant epitopes located at the carboxyl terminus, known to provoke robust immune responses and pulmonary inflammation. We have developed an mRNA vaccine harnessing this dominant antigenic epitope and assessed its protective immunity in BALB/c mice against M. pneumoniae infection. The vaccine elicited potent humoral and cellular immune responses, effectively diminishing inflammation. It notably decreased IL-6 levels in the lungs of infected mice and concurrently elevated IL-4, IL-10, and IFN-γ levels post-immunization. The vaccine also reduced pathological changes in the lungs and the M. pneumoniae DNA copy numbers in the infected animals. Collectively, these findings underscore the mRNA vaccine's remarkable immunogenicity and protective potential against M. pneumoniae infections, offering valuable insights for the development of mRNA vaccines targeting mycoplasma infections.IMPORTANCEM. pneumoniae, a bacteria without a cell wall, is known for causing pneumonia and is resistant to penicillin. The increasing prevalence of macrolide-resistant strains has complicated treatment options, emphasizing the need for new strategies. Our research explores an mRNA vaccine candidate that targets the P1 adhesin of M. pneumoniae, a protein critical for the bacteria's interaction with host cells. In a mouse model, this vaccine has shown potential by inducing immune responses and suggesting a possible reduction in inflammation, as indicated by changes in cytokine levels and lung pathology. While further research is required, the vaccine's preliminary results hint at a potential new direction in managing mycoplasma infections, offering a promising avenue for future therapeutic development. This study contributes to the ongoing search for effective preventive measures against M. pneumoniae.

Characterization of serum and brain cytokine levels following prolonged binge-like methamphetamine self-administration and cued methamphetamine seeking.

Methamphetamine (METH) use is associated with peripheral and brain inflammation that can contribute to METH-associated toxicity and heightened cue reactivity. However, the persistence of these phenomena, especially with regards to changes in brain proinflammatory cytokine levels, is not yet clear. In this study, we determined the effects of repeated binge-like METH self-administration (96-h/week for 3weeks) followed by cued drug seeking for up to 60days into abstinence in male and female rats. Serum cytokine levels were assessed prior to cued drug seeking tests on days 21 and 60 of abstinence, and cytokine levels in the prefrontal cortex (PFC) and dorsal striatum (DStr) were assessed on the day following that last cued seeking test. We observed robust levels of METH intake in both sexes as well as a gradual increase in magnitude of METH seeking across abstinence that did not differ between sexes. Magnitude of METH seeking on days 10 and 60 were positively correlated with prior total drug intake. Sex- and region-dependent changes in various chemokines and interleukins were observed in the PFC and DStr, as were sex- and time-dependent changes in serum cytokine levels, with the largest number of cytokines altered on day 60 in male animals. Serum levels of IL-6 were positively correlated with brain levels of this cytokine, but serum levels of this and other cytokines did not correlate with the magnitude of METH seeking. These findings suggest that binge-like METH intake produces persistent yet divergent central and peripheral immune responses that extend well into abstinence.

Circulating immune biomarkers correlating with response in patients with metastatic renal cell carcinoma on immunotherapy.

As multiple front-line immune checkpoint inhibitor (ICI)-based combinations are approved for metastatic renal cell carcinoma, biomarkers predicting for ICI responses are needed past clinical prognostication scores and transcriptome gene expression profiling. Circulating markers represent opportunities to assess baseline and dynamic changes in immune cell frequency and cytokine levels while on treatment. We conducted an exploratory prospective correlative study of 33 patients with metastatic clear cell renal cell carcinoma undergoing treatment with ICIs and correlated changes in circulating immune cell subsets and cytokines with clinical responses to treatment. Cell frequencies and cytokine levels were compared between responders and non-responders using unpaired parametric t tests, using a pre-specified level of significance of p<0.05. Classical monocyte subsets (CD14+ CD16-), as well as seven cytokines (IL-12/23 p40, macrophage inflammatory protein-1a, macrophage inflammatory protein-1b, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, IL-8, and TNF-alpha) were higher at baseline for responding versus non-responding patients. Dynamic changes in thymus- and activation-regulation chemokine (TARC), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) also correlated with patients with ICI response. In summary, macrophage activating agents were observed to be important in ICI response and may highlight the importance of the innate immune response in ICI responses.

Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation.

Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver. Therefore, we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases. To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases. We established a mouse biliary disease model by directly connecting the gallbladder and duodenum, enabling ascending infection into the biliary tract without traversing the sphincter of Oddi. In the cholecystoduodenal anastomosis mouse model, we observed impaired epithelial structure, wall thickening, and macrophage recruitment in the gallbladder. Despite the absence of postoperative antibiotics, we detected no changes in serum proinflammatory cytokine levels, indicating no systemic inflammation. Moreover, patency between the gallbladder and duodenum was confirmed via common bile duct ligation. Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection, which significantly increased proinflammatory cytokine mRNA expression in the liver, duodenum, and ileum. These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum, leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans. The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.

P05 Evaluation of changes in serum cytokine (TNFα, IFNα2, IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-23, IL-33, and MCP-1) values in biologic-naive psoriasis patients during biologic agent use

Abstract Psoriasis is an immune-mediated chronic inflammatory skin disease. Proinflammatory cytokines have an important role in the pathogenesis. Current treatments mainly act on TNF-α, IL-12, IL-17 or IL-23 pathways. It is thought that determination of cytokine levels before treatment can be used as useful biomarkers for monitoring disease activity and personalized treatment selection. The aim of this study is to contribute to the establishment of biomarkers that can help predict disease severity, treatment response and disease prognosis in patients with psoriasis and also compare healthy controls. We analysed the changes in serum levels of cytokines (TNFα, IFNα2, IFNγ, IL-1β, IL-6, IL-8, IL-10, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-23, IL-33, MCP-1) before and 4 months after treatment with biological agents in 40 bio-naive psoriasis patients and 15 healthy subjects. Flow cytometry method [LEGENDplex™ Multi-Analyte Flow Assay Kit Human Inflammation Panel 1, 13 Plex with V-bottom Plate (BioLegend, San Diego, CA, USA)] was used for the determination of cytokine levels. Clinical and demographic information, including PASI (psoriasis area and severity index) and DQLS (Dermatology Quality of Life Scale) scores were recorded. In addition, acute phase reactants (CRP, ESR, ferritin, albümin) were measured before and after 4 months of treatment. The data obtained were analysed using NCSS 2007 software. PASI and DQLS scores at the fourth month of treatment were found to be significantly lower compared with the onset (P = 0.000, P = 0.0001, respectively). When cytokine values were analysed; IFN-γ levels of the patients increased after treatment (P = 0.007). Pre-treatment IL-33 and IL-1β levels of the patients were lower than healthy subjects (P = 0.045), but there was no difference between the mean levels of these cytokines before and after treatment. Among the biologic agents, IL-17A levels were found to be lower only in patients using secukinumab (P = 0.022). Pre-treatment and post-treatment IL-17A difference of the secukinumab group was higher than the other drugs (P = 0.004, P = 0.009), while no statistical difference was observed between the other biologic agents (P &amp;gt; 0.05). There was no correlation between age at disease onset, PASI and DQLS and cytokine levels. The ESR, CRP, and ferritin values of the patients were higher than the healthy controls before treatment (P = 0.011, P = 0.022, and P = 0.037, respectively). However, only ESR decreased after treatment in psoriasis patients (P = 0.027). In this study, no significant differences were found in serum cytokine levels. However, the literature shows that while serum levels may remain unchanged, tissue levels can be significantly different. Future studies should include cytokine analyses in both serum and tissue levels.

Ameliorative Effect of Ginsenoside Rc on 5-Fluorouracil-Induced Chemotherapeutic Intestinal Mucositis via the PI3K-AKT/NF-κB Signaling Pathway: In Vivo and In Vitro Evaluations.

5-Fluorouracil (5-Fu) is a chemotherapeutic agent widely used to treat various cancers, which causes intestinal mucositis as a common side effect. Ginsenoside Rc, an active compound with anti-inflammatory, antioxidant, immunomodulatory, and antitumor properties, has protective effects against chemotherapy-induced mucositis caused by 5-Fu. This study aims to evaluate the protective effects of Rc on 5-Fu-induced chemotherapy-related mucositis and to elucidate its underlying mechanisms. In vivo experiments were conducted to measure intestinal permeability and assess the effects of Rc on body weight loss, diarrhea, and intestinal pathology induced by 5-Fu. Network pharmacology was also employed to explore potential mechanisms. In vitro, IEC-6 cell models were used to validate the cytoprotective effects of Rc, including assessments of cell viability, apoptosis, lactate dehydrogenase (LDH) release, and changes in inflammatory cytokine levels. The results indicate that Rc significantly ameliorated body weight reduction, diarrhea, and intestinal damage in mice treated by 5-Fu. Rc significantly mitigated 5-Fu-induced cellular damage by reducing levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α and decreasing apoptosis and cell permeability. Western blot analysis revealed that Rc upregulated the expression of Bcl-2 and tight junction proteins and downregulated the expression of Bax. Furthermore, Rc exerts anti-inflammatory and anti-apoptotic effects through PI3K-AKT and NF-κB signaling pathways. In conclusion, ginsenoside Rc demonstrated significant protective effects against 5-Fu-induced intestinal mucositis via the PI3K-AKT/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for chemotherapy-related mucositis.

Early introduction of IL-10 weakens BCG revaccination’s protection by suppressing CD4+Th1 cell responses

BackgroundThe Bacillus Calmette-Guérin (BCG) vaccine, currently the sole authorized vaccine against tuberculosis (TB), demonstrates limited effectiveness in safeguarding adolescents and adults from active TB, even when administered as a booster with either BCG itself or heterologous vaccine candidates. To effectively control the persistent epidemic of adult TB, it is imperative to investigate the mechanisms responsible for the suboptimal efficacy of the BCG prime-boosting strategy against primary Mycobacterium tuberculosis (M.tb) infection.MethodsC57BL/6J mice were immunized with the BCG vaccine either once or twice, followed by analysis of lung tissue to assess changes in cytokine levels. Additionally, varying intervals between vaccinations and detection times were examined to study IL-10 expression across different organs. IL-10-expressing cells in the lungs, spleen, and lymph nodes were analyzed through FACS and intracellular cytokine staining (ICS). BCG-revaccinated IL-10−/− mutant mice were compared with wild-type mice to evaluate antigen-specific IgG antibody and T cell responses. Protection against M.tb aerosol challenge was evaluated in BCG-revaccinated mice, either untreated or treated with anti-IL-10R monoclonal antibody.ResultsIL-10 was significantly upregulated in the lungs of BCG-revaccinated mice shortly after the booster immunization. IL-10 expression peaked in the lungs 3–6 weeks post-revaccination and was also detected in lymph nodes and spleen as early as 2 weeks following the booster dose, regardless of the intervals between the prime and booster vaccinations. The primary sources of IL-10 in these tissues were identified as macrophages and dendritic cells. Blocking IL-10 signaling in BCG-revaccinated mice—either by using IL-10−/− mutant mice or administering anti-IL-10R monoclonal antibody increased levels of antigen-specific IFN-γ+ or IL-2+ CD4+ T cells, enhanced central and effector memory CD4+ T cell responses, and provided better protection against aerosol infection with 300 CFUs of M.tb.ConclusionOur findings are crucial for formulating effective immunization strategies related to the BCG vaccine and for developing efficacious adult TB vaccines.Graphical abstract

Blood cytokine levels in patients with combined and multiple skeletal injuries

Introduction. With regard to changes in blood cytokine levels and the development of posttraumatic complications, monitoring of these parameters may help in understanding the role of blood cytokines in the development of inflammatory reactions after trauma and the potential possibility of using them as biomarkers to predict the severity of the systemic inflammatory response. The purpose of the study: to investigate the role of cytokines in the development of inflammatory reactions after trauma and the possibility of using them as biomarkers. Material and methods. The study included 228 patients with combined trauma of organs of several cavities and skeletal traumas. IL-8, IL-10, TGFβ, and IL-4 concentrations were determined by enzyme immunoassay method in strict accordance with the manufacturer's instructions (R&amp;D Systems, USA). Results and Discussion. As a result of the study, IL-6 increased in patients on day 1–2 after injury, as did IL-8, IL-10, TGFβ, and IL-4. IL-6, IL-8, IL-10, and TGFβ indices in patients remained high on day 5–7 and tended to increase, while, on the contrary, IL-4 index tended to decrease. In our study we found the increase of TGFβ-1 index 1–2 days after the patient's injury and it reached the maximum values (TGFβ-1–134 ng/ml). Conclusion. Changes in the indices of the studied blood cytokines in trauma patients revealed an imbalance in inflammatory reactions after trauma, which was more pronounced in patients in severe conditions and in patients with complications.

Deranged cytokine levels are linked to cancer-related cognitive impairment in lymphoma patients receiving R-CHOP chemotherapy

Cancer-related cognitive impairment (CRCI) is a significant issue commonly observed following chemotherapy treatment. The study aimed to investigate the changes in cognitive function and their association with IL-6, IL-1β, and IL-10 levels before and after R-CHOP chemotherapy over six cycles. Seventy chemotherapy naïve, newly diagnosed lymphoma patients were enrolled. Cognitive functions and inflammatory cytokines were assessed at baseline (TP1), after 3rd cycle (TP2), and after 6th cycle (TP3). Patients, with mean age of 44.17 ± 13.67 years, showed significantly increased levels of IL-6 and IL-1β and decreased IL-10 levels over time (p < .001). On the Montreal Cognitive Assessment (MoCA), scores of domains such as executive functioning (p = .002), attention (p < .001), language (p < .001), recall (p = .005), and orientation (p < .001) significantly decreased post six cycles of R-CHOP chemotherapy. Correlation analysis at TP2 indicated a positive association between elevated IL-6 levels with a decrease in MoCA scores indicating a decline in cognitive function (ρ = 0.68, p < .001). At TP3, no association of MoCA scores with IL-6 and IL-1β was observed. Decreased IL-10 levels showed a weak association with decreased MoCA scores at TP2 and TP3 ( ρ = 0.2, p = .09; for TP3, ρ = 0.16, p = .17), but this was not significant. In summary, the findings of the present study highlight significant cognitive decline and changes in inflammatory cytokine levels following six cycles of R-CHOP. Objective cognitive assessments may be done to detect CRCI in patients treated with R-CHOP.

Molecular mechanisms of obesity predisposes to atopic dermatitis.

Obesity is a prevalent metabolic disease that reduces bacterial diversity, colonizes the epidermis with lipophilic bacteria, and increases intestinal pro-inflammatory species, all of which lead to impaired epithelial barriers. Adipose tissue secretes immunomodulatory molecules, such as adipokines, leptin, and adiponectin, which alters the morphology of adipocytes and macrophages as well as modulates T cell differentiation and peripheral Th2-dominated immune responses. Atopic dermatitis (AD) and obesity have similar pathological manifestations, including inflammation as well as insulin and leptin resistance. This review examines the major mechanisms between obesity and AD, which focus on the effect on skin and gut microbiota, immune responses mediated by the toll like receptor (TLR) signaling pathway, and changes in cytokine levels (TNF-a, IL-6, IL-4, and IL13). Moreover, we describe the potential effects of adipokines on AD and finally mechanisms by which PPAR-γ suppresses and regulates type 2 immunity.

Co-Colorectal cancer stem cells employ the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia

Colorectal cancer (CRC) ranks as China’s second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions. The impact of this co-culture was evaluated using CCK8 assays for NK cell viability, ELISA for cytokine level changes, and flow cytometry for assessing NK cell apoptosis and activation. Comprehensive metabolomic and transcriptomic analyses were also performed to identify key genes and metabolites involved in the interaction between CCSCs and NK cells Co-culture of CCSCs with NK cells under hypoxia reduced NK cytotoxicity, increased NK apoptosis, and altered cytokine secretion by decreasing IFN-γ and TNF-α levels while increasing IL-6. Transcriptomic and metabolomic analysis identified 4 genes (FADS1, ALDH3A2, GCSH, MTCL1) and 3 metabolites (glyoxylic acid, spermine, DDA) as significant. Interfering with FADS1 counteracted the suppression of IFN-γ and TNF-α induced by CSC cells. Curiously, this inhibition caused by si-FADS1 could be neutralized by the addition of exogenous DDA. Co-culturing with NK cells notably increased spermine levels. Exogenous spermine resulted in a significant reduction in HT-29 cell death rates at 32 µM, 64 µM, and 128 µM, compared to NK cells without spermine. Our research explored CCSCs employed the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.

SARM1 deficiency induced depressive-like behavior via AMPKα/p-eEF2 axis to synapse dysfunction

Sterile Alpha and TIR Motif Containing 1 (SARM1) are proteins implicated in various neurological processes; however, their role in depression remains unexplored. This study investigated the contribution of SARM1 to depressive-like behaviors in a chronic stress-induced depression model and SARM1 knockout (KO) mice. Depressive-like behaviors were assessed using a battery of behavioral tests, including the Open Field Test (OFT), the Forced Swim Test (FST), the Sucrose Preference Test (SPT), and the Tail Suspension Test (TST). Mitochondrial energy metabolism alteration, cytokine level changes, and other related molecular signaling protein expression were evaluated using ELISA and western blotting techniques to investigate the underlying mechanisms. Behavioral assessments (OFT, FST, SPT, TST) revealed depressive-like phenotypes in SARM1 KO mice, accompanied by altered mitochondrial energy metabolism (NAD+, ATP) in the cortex. Intriguingly, SARM1 depletion led to peripheral inflammation, as evidenced by elevated cytokine levels in plasma but not in brain regions (cortex). In addition, we found dysregulated energy metabolism, AMPK signaling, and synaptic plasticity in the cortex of SARM1 KO mice. Notably, AICAR (Acadesine), an AMPK activator, ameliorated depressive-like behaviors and synaptic dysfunction, while Compound C, an AMPK inhibitor, reversed these effects. Additionally, NH125, an eEF2 kinase inhibitor, improved depressive-like behaviors in SARM1 KO mice. These findings demonstrate that SARM1 is critical in regulating depressive-like behaviours through the AMPKα/p-eEF2 signaling pathway. Targeting AMPK signaling and synaptic function may offer novel therapeutic avenues for depression.

Prognostic role of serum cytokines level in non-small cell lung cancer patients with anti-PD-1 and chemotherapy combined treatment.

Chemotherapy combined with PD-1 inhibitor treatment has revolutionized the standard of care for patients with NSCLC. However, the benefit is not universal, highlighting the need for precise prediction factors. Given their relationship with the immune system and non-invasive nature, serum cytokines are potential candidates for predicting the clinical effects of chemoimmunotherapy. Our study aims to evaluate the association of serum cytokines with the prognosis of patients with NSCLC treated with chemoimmunotherapy. Levels of 10 serum cytokines were detected in 60 NSCLC patients receiving chemotherapy plus PD-1 inhibitor-based treatment. Of these, dynamic samples from 19 patients were collected at baseline and after two treatment cycles. Their association with patients' clinicopathological characteristics, PFS and OS was described and investigated using survival analysis, cox regression and time-dependent ROC analysis. Preliminary evaluation of changes in cytokine levels associated with treatment response was conducted. Patients with lower baseline levels of serum IL-6, IL-5, IL-8, TNF-α and IL-10 had longer PFS, while patients with higher levels of IL-4 had longer PFS. Patients with lower levels of serum IL-6, IL-8, IL-22, TNF-α and IL-10 had longer OS, while patients with higher levels of IL-4 had longer OS. Multivariate analysis suggested that higher IL-6 and IL-5 levels were associated with poorer PFS, and higher IL-6 levels were associated with dismal OS. Additionally, changes in serum cytokine levels could be associated with treatment response. Our study suggests that serum cytokines, specifically IL-6, IL-5, IL-8, TNF-α, IL-10, and IL-4, are potential prognostic factors for patients with NSCLC receiving chemotherapy plus PD-1 inhibitor treatment.

An Early Increase in IL-10 and TNF-α Levels Following Atezolizumab Plus Bevacizumab Treatment Predicts Survival in Advanced Hepatocellular Carcinoma Patients: A Prospective Cohort Study

Background/Objectives: Reliable biomarkers for predicting outcomes in hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev) are still lacking. Cytokines, which play a crucial role in immune regulation and HCC progression, have potential as predictive markers, but data supporting their use are limited. This study aimed to evaluate the impact of early changes in cytokine levels on the clinical outcomes of advanced HCC patients. Methods: We prospectively enrolled 32 advanced HCC patients, collecting blood samples before the first and second Ate/Bev treatments. These samples were analyzed for IL-2, IL-6, IL-10, IL-12, IL-17, IFN-γ, and TNF-α levels to assess changes post-treatment. The primary outcome was overall survival, with a secondary focus on progression-free survival (PFS) at 6 months. Results: The mean age of the participants was 64.2 years, with the majority being male (93.8%). Patients showing increased IL-10, IL-17, and TNF-α levels had significantly better survival (p &lt; 0.05) and marginally improved PFS compared to those with decreased cytokine levels. Interestingly, a positive correlation was noted between changes in IL-10 and TNF-α levels (p = 0.009). Furthermore, a multivariable analysis revealed that increased levels of IL-10 and TNF-α were significant predictors of enhanced survival (hazard ratio, 0.07; 95% confidence interval, 0.01–0.46; p = 0.005). Conclusions: An early increases in IL-10 and TNF-α after Ate/Bev treatment may serve as effective biomarkers for clinical outcomes in advanced HCC patients.

A study on subcutaneous infection model of colibacillosis in broilers: Selected immunological and hematological aspects

Colibacillosis is still a major challenge to poultry industry. This study examined selected immune and hematological features of broilers experimentally infected with E. coli via subcutaneous (sc) route. Fifty-one 5-week-old chickens were randomly assigned to three groups: two controls (NC and SCC) and one experimental (SC) group. The SC group was inoculated by O2 E. coli suspension via sc route in the inguinal region. Three days after inoculation, blood sampling was performed. Bacterial count of liver was determined. Histopathological samples of liver, lung, spleen, thymus, and bursa were also collected. Serum total protein and globulin significantly increased in birds of SC group as compared to control birds (P < 0.05). Birds in SC group also showed decreased albumin/globulin ratio. Serum levels of IL-6, IL-10, and IFN-γ remained statistically the same among groups. Lymphocytosis, monocytosis, thrombocytosis and heterophilia were present in SC group. Heterophils/lymphocytes ratio increased in SC birds. Left shift was observed in SC group with cells showing vacuolated cytoplasm that contained toxic granules. Histologically, lung involvement was less severe than liver. Lymphoid depletion was present in all examined lymphoid organs. E. coli growth was observed in liver samples from SC group but not in control birds. In conclusion, using sc route for induction of colibacillosis was associated with a systemic inflammatory response in broilers and histopathological lesions of thymus, bursa, and spleen three days post-infection. It seems that detection of changes in serum cytokine levels (IL-6, IL-10, and IFN-γ) should be performed in earlier hours of the disease in this model.

Dynamics of Peripheral Lymphocyte Subsets from Birth until Old Age

The immune system is inexperienced before birth and tends to be tolerogenic, rather than immunogenic. After birth, the adaptive immune system develops while facing microbial challenges, but it can become impaired as old age progresses and persistent inflammation can lead to chronic morbidity, disability and frailty. To investigate the potential contributions of lymphocyte subsets to immunity from birth until old age, we enumerated circulating innate and conventional lymphocytes and measured serum cytokine levels in 10 cord blood samples and in peripheral blood from 10 healthy term neonates, 23 healthy school-age children, 25 young adults and 11 older subjects. Flow cytometric analysis revealed that B cell frequencies increase during childhood and gradually decrease into adulthood, whereas natural killer cell frequencies increase throughout life. T cell frequencies remained relatively constant throughout life, as did their expression of CD4 and CD8. However, all four innate T cell populations studied—invariant natural killer T cells, mucosa-associated invariant T cells and the Vδ1 and the Vδ2 subsets of γδ T cells—were extremely rare in cord blood and in peripheral blood of neonates, but they expanded after birth reaching highest levels in adulthood. Analysis of serum cytokine levels revealed that proinflammatory and T helper type 1 (Th1) cytokine levels increase in adulthood, whereas Th2 and Th17 cytokine levels remain relatively constant. These changes in lymphocyte numbers and cytokine levels across the lifetime are likely to affect immunocompetence, leaving newborn and elderly people susceptible to infection, cancer and immune-mediated disease.

Histological Improvement and Cytokine Levels Reduction in Patients with Oral Lichen Planus after Photobiomodulation Therapy.

Background: Oral lichen planus (OLP) is a mucocutaneous disease associated with the formation of symptomatic lesions in the mouth that are often refractory to treatment. An as-yet-unknown antigen triggers an inflammatory reaction in which various immune and non-immune cells release multiple cytokines that contribute to disease progression. The ability of photobiomodulation (PBM) to reduce the symptoms and signs of the disease has been shown, but little is known about its molecular and cellular effects. The aim of this study was to evaluate changes in pro-inflammatory cytokine levels and in histological findings in OLP patients treated with photobiomodulation therapy. Methods: Twenty OLP patients underwent PBM with diode laser (810 nm), (0.50 W, 30 s, 1.2 J/cm2), 3 times weekly for a month. Pain level and clinical scores of lesions were recorded before and after therapy. Salivary levels of IL-1β, IL-6, and TNF-α in OLP patients were measured before and after PBM and compared with those of 10 healthy controls. Biopsies were taken at the beginning and end of treatment to assess pathomorphological changes. Results: PBM significantly reduced the level of pain and clinical scores of the lesions. Salivary levels of IL-1β, IL-6, and TNF-α in OLP patients were significantly higher compared to those in healthy controls and decreased after therapy. 60% of the post-treatment OLP biopsies demonstrated histological improvement, characterized by inflammatory infiltrate reduction (50%), epithelial hyperplasia reduction (30%), epithelial thickening (15%), or epidermal-dermal attachment repair (5%). Conclusion: The effectiveness of PBM therapy in OLP patients was confirmed at the clinical, molecular, and histomorphological levels.