Serum Cytokine Concentrations Research Articles

Modified Xiao-Qing-Long-decoction prevents inflammation and promotes Nur77 expression in mice with acute respiratory distress syndrome by inhibiting HDAC7 expression

Context Modified Xiao-Qing-Long-decoction (MXQLD) is believed to have the potential to alleviate lung diseases. Objective We explored the effects and mechanisms of MXQLD in acute respiratory distress syndrome (ARDS). Materials and methods Thirty male C57BL/6 mice were randomized into sham (distilled water), model (distilled water), MXQLD (1 g/kg MXQLD), DEX (distilled water + 0.7 mg/kg dexamethasone), MXQLD + oe-HDAC7 (HDAC7 over-expression + 1 g/kg MXQLD) groups. Except for HDAC7 over-expression on day 0 and dexamethasone injection on day 12, all treatments were administered every two days from day 0 to day 10. On day 12, except for the sham group, all mice underwent cecal ligation and puncture surgery to establish ARDS models. After surgery, pulmonary functions, protein concentration of bronchoalveolar lavage fluid (BALF) and lung tissue morphology in mice were detected. Furthermore, pro-inflammatory cytokine concentrations (IL-6, IL-1β, and TNF-α) in BALF supernatant and serum were quantified. Additionally, HDAC7, Nur77, ZO-1, occludin, and claudin protein expressions were detected. Results MXQLD treatment improved pulmonary functions and alleviated lung injury for ARDS mice. Furthermore, MXQLD treatment decreased protein concentration in BALF, and inhibited pro-inflammatory cytokine release in BALF supernatant and serum for ARDS mice. Additionally, MXQLD treatment down-regulated HDAC7 expression, but up-regulated Nur77, ZO-1, occludin, and claudin expressions for ARDS mice. Importantly, the preventive effects of MXQLD in ARDS mice were reversed by HDAC7 over-expression. Discussion and conclusion MXQLD may prevent inflammation and promote Nur77 expression in ARDS by inhibiting HDAC7 expression, indicating that MXQLD may be a promising drug for preventing ARDS.

Characterizations of cytokines and viral genomes in serum of patients with Dabie bandavirus infection

BackgroundTen cases with Dabie bandavirus infection were identified in Suzhou City, China, from April 2023 to August 2024. All 10 cases were hospitalized patients, and three died. We detected and analyzed the cytokine concentrations and viral genomes in the serum samples of these patients to identify the possible causes of the patients’ deaths and to analyze the viral genetic characteristics.MethodsBlood serum specimens were obtained from the 10 individuals with Dabie bandavirus infection in Suzhou City. The specific nucleic acid of Dabie bandavirus was detected using a real-time reverse transcription polymerase chain reaction assay (RT-qPCR). The cytokine concentrations in serum were detected by micro enzyme-linked immunosorbent assay (ELISA). The genomes of Dabie bandavirus were amplified using a designated primer pool. The DNA sequencing libraries were prepared using a ligation method. The sequencing process was performed using a Nanopore GridION X5 instrument. Phylogenetic trees for the L, M, and S segments of Dabie bandavirus were constructed using the maximum likelihood (ML) method in MEGA 11 software, with the bootstrap value set at 1,000.ResultsAll 10 patients with Dabie bandavirus infection exhibited a severe clinical course, resulting in three fatalities. The cytokine concentrations of CCL2, GM-CSF, IFN-γ, IL-1β, IL-6, IL-8, and TNF-α were significantly elevated in the fatal patients compared with the recovered cases; all p-values for these cytokine analyses were under 0.05. The Dabie bandavirus strains identified in Suzhou belonged to three distinct genotypes: A, B, and F. The nucleotide identities for the L, M, and S segments were 95.65%–99.76%, 93.73%–99.81%, and 94.62%–99.88%, respectively. The average evolutionary rate of segment S was higher than that of segment M and segment L. The ratio of dN/dS in the membrane protein was the highest. SZ03-TXF was a recombinant strain with the location of possible breakpoints at nucleotides 795 and 1,432 in the CDS region of the L segment.ConclusionA recombination event was identified in SZ03-TXF strain. High viral load and cytokine storm may be associated with the case fatality of Dabie bandavirus infection. We should strengthen the monitoring of nucleotide substitutions and conduct health education for high-risk populations so as to effectively prevent and control an epidemic of the Dabie bandavirus infection in the future.

Assessment of the Utility of Selected Inflammatory Markers in Correlation with Magnetic Resonance Enterography (MRE) Findings in the Diagnosis of Crohn's Disease.

Crohn's Disease (CD) is a chronic inflammatory bowel disease affecting the gastrointestinal tract. The search continues for new markers for assessing the activity of CD. Among them, pro-inflammatory and anti-inflammatory cytokines appear promising. We performed the analysis of cytokine concentrations in blood serum using the Bio-Plex Multiplex system (Bio-Rad), and their correlations with radiological parameters were assessed by magnetic resonance enterography (MRE), and fecal calprotectin levels were measured quantitatively by ELISA and clinical evaluation according to the Crohn's Disease Activity Index (CDAI). Our study found that measuring cytokine serum concentrations can be a valuable tool in the diagnosis and treatment of CD. Positive correlations were reported between contrast enhancement on DCE-MRE and the concentrations of PDGF-BB and RANTES. Also, a positive correlation was found between the delayed-phase of DCE and IL-10 concentration, a strong negative correlation between the delayed-phase of DCE and IL-12 concentration, and a strong positive correlation between the delayed-phase of DCE and RANTES concentrations. A strong positive correlation was also observed between the thickness of the intestinal wall on T2-weighted images and RANTES concentration. Therefore, concentrations of PDGF-BB, RANTES, IL-10 and IL-12 are promising markers of CD activity. The study also demonstrated significant correlations between the severity of disease activity assessed by the CDAI and the concentrations of IL-5, IL-8 and IL-9, as well as positive correlations between the levels of fecal calprotectin and the concentrations of IL-1RA and VEGF. Therefore, the levels of IL-5, IL-8, IL-9, VEGF and IL-1RA may be useful markers in the diagnosis and clinical assessment of disease activity.

Systemic regulatory factors of angiogenesis in multiple uterine myoma

Uterine leiomyomas (UL) are benign uterine tumors. Hypertrophic increase in muscle mass in LM is accompanied by development of vascular networks, which are regulated by the balance of pro-angiogenic factors, e.g., VEGF-A. Moreover, a number of inflammatory molecules exert pro-angiogenic effects, especially, IL-1β, IL-8, etc. The spectrum of their activity may overlap, being regulated by other cytokines. The aim of our work was to assess serum concentrations of cytokines actively involved in vascular network growth in the patients with multiple uterine fibroids, as compared with data obtained in conditionally healthy women. The survey included 178 females: 89 women (23-60 years old) with uterine fibroids, and 89 conditionally healthy age-matched women (22-61 years old). The levels of TNFα, IL-1β, IL-4, IL-6, IL-8, IL-10 and VEGF-A were detected by ELISA technique (Vector-Best, Russia). Statistical analysis was carried out using the IBM SPSS Statistics 23 (USA). Serum levels of IL-6, TNF and IL-8, were higher among patients compared with healthy women. The dependence of VEGF level on the number of myoma nodes has been established: VEGF serum level was higher in patients with multiple tumor nodes. In healthy women, an increase in TNFα level showed direct correlation with higher serum level of IL-6. Correlation with VEGF level was weakly negative. In leiomyoma, these relationships persist for IL-6, IL-8, VEGF levels. The obtained data are of practical importance not only as potential prognostic criteria for development of the uterine myoma at preclinical stage, but also as additional laboratory indexes for differential diagnostics, in particular when discerning uterine leiomyoma, the most common benign myomatous tumor of uterus, from malignant uterine leiomyosarcomas.

Comparative Performance of Ante-Mortem Diagnostic Assays for the Identification of Mycobacterium bovis-Infected Domestic Dogs (Canis lupus familiaris).

The domestic dog (Canis lupus familiaris) is a competent host for Mycobacterium (M.) bovis infection but no ante mortem diagnostic tests have been fully validated for this species. The aim of this study was to compare the performance of ante mortem diagnostic tests across samples collected from dogs considered to be at a high or low risk of sub-clinical M. bovis infection. We previously tested a total of 164 dogs at a high risk of infection and here test 42 dogs at a low risk of infection and 77 presumed uninfected dogs with a combination of cell-based and/or serological diagnostic assays previously described for use in non-canid species. The interferon-gamma release assay (IGRA) using peripheral blood mononuclear cells (PBMCs) identified the highest number of test-positive animals (85, 52%), with a suggested specificity of 97.3%, whilst a whole-blood IGRA was found to be unreliable. The production of antigen-specific tumour necrosis factor-alpha (TNF-α) by PBMC in response to a cocktail of ESAT-6 and CFP-10 peptides correlated very strongly with the overall IGRA results, suggesting future diagnostic potential. All three serological assays employed in this study (Idexx M. bovis Ab ELISA, [Idexx Laboratories, Westbrook, ME, USA], DPP VetTB lateral flow assay [Chembio, Medford, NY, USA], and comparative PPD ELISA [in-house]) identified seropositive dogs but, overall, the test-positive rate for the serological assays was only one third that of the cellular-based assays. Circulating serum cytokine concentrations of interferon gamma and TNF-α were not statistically different between the high- and low-risk groups of dogs. While many dogs in the high-risk group had serum biochemical abnormalities, these did not correlate with the findings from the diagnostic TB tests. This study demonstrates, for the first time, the utility of two cellular and three serological assays for detecting sub-clinical M. bovis infections of dogs. Whilst the data suggest a high test specificity for all assays evaluated, further work is needed to validate the sensitivity and specificity of individual or combinations of tests using sufficient numbers of dogs of a known infection status.

Прогностическое значение экспрессии галектина-1 опухолевыми плазматическими клетками и концентрации некоторых сывороточных цитокинов (IL-2, IL-6, TNF) у пациентов с моноклональной гаммапатией неопределенного значения и множественной миеломой

AIM. To study the prognostic value of the galectin-1 expression by bone marrow (BM) tumor plasma cells (PCs) and the concentration of serum cytokines (interleukins [IL-2, IL-6] and tumor necrosis factor [TNF]) in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (ММ). MATERIALS & METHODS. The trial enrolled 129 patients: 77 patients with newly diagnosed MM (median age 64 years) and 52 patients with MGUS (median age 62.5 years) followed-up at the Republican Scientific and Practical Center for Radiation Medicine and Human Ecology from 2018 to 2023. All patients underwent general clinical examination as well as BM aspirate cytology with myelogram and iliac BM core biopsy with immunohistochemical (IHC) analysis of BM biopsy. RESULTS. In the BM biopsy, the IHC analysis revealed a significant increase of galectin-1 expression (measured by expressing tumor PC count) in MM vs. MGUS patients (p < 0.001). Galectin-1 expression defined as expressing tumor PC count was significantly higher in patients with progressing MGUS compared to progression-free MM patients (p < 0.001). The median galectin-1 expression level was 8.5 % (Q25 0.2 %; Q75 15.7 %) in progression-free MGUS patients and 37.4 % (Q25 24.7 %; Q75 64.0 %) in progressing MGUS patients. Among MM patients, no significant differences were identified either in those with and without tumor progression. The IHC analysis of BM core biopsies in MM patients showed that high galectin-1 expression level is associated with pronounced vasculature but not with fibrotic changes, it also identified an increase in serum concentrations of IL-2 and TNF as well as a direct correlation with β2-microglobulin level. With MGUS progression into ММ, there was a direct correlation between galectin-1 expression level and serum M-protein. An increase of IL-2 concentration was registered only when MGUS progressed into ММ. CONCLUSION. The results of this study indicate the evidence of a high level of galectin-1 expression by tumor PCs in MM. In MGUS, an increase of galectin-1 expression by clonal BM PCs was associated with the disease progression. Galectin-1 expression by clonal BM PCs can well be clinically used as a marker for MGUS progression into MM.

Immunomodulatory effects of supercritical CO2 extracted oils from Portulaca oleracea and Perilla frutescens (PPCE) in healthy individuals: a randomized double-blind clinical trial.

The human immune system plays a crucial role in defending the body against various infections, viruses, and external substances, contributing to overall well-being. However, an imbalance in the immune system can lead to increased susceptibility to infections, impacting overall health. Preclinical investigations suggest the potential application of Portulaca oleracea L. and Perilla frutescens var. japonica Hara seed complex extract (PPCE) as a potent biological response modifier in terms of immunity. However, the safety and efficacy of PPCE in boosting immune function have not been investigated clinically. The present study aims to evaluate the safety and efficacy of PPCE on the immune system in healthy adults. An 8-week randomized, double-blinded, placebo-controlled cross-over clinical trial was adopted for the study. Study participants were administered either 1080 mg day-1 of a PPCE supplement or a placebo. The study assessed the Natural Killer (NK) cell activity as the primary outcome measure. Serum concentrations of cytokines (IL-6, IL-12, IFN-γ, TNF-α) and a questionnaire-based assessment of upper airway infection were the secondary outcomes. At the end of the 8 weeks, NK cell activity significantly improved in the PPCE group compared to the placebo group (p < 0.05). Similarly, the concentrations of IFN-γ and IL-12 significantly increased (p < 0.05). However, there were no significant differences between the two groups in the cytokines IL-6 and TNF-α. Additionally, no adverse effects were observed during the trial. These findings suggest that PPCE supplementation is safe and potentially benefits immune stimulation by enhancing NK cell activity and inducing the production of Th-1 type cell-stimulating cytokines like IL-12 in healthy individuals.

Precision medicine using molecular-target drugs in psoriatic arthritis.

Psoriatic arthritis (PsA) presents various clinical manifestations, including skin lesions, peripheral arthritis, axial involvement, enthesitis, nail involvement, dactylitis, and uveitis. In addition, it causes a high incidence of lifestyle-related diseases and an increase in cerebrovascular and cardiovascular events. As the pathology of PsA has been clarified, molecular-targeted drugs targeting tumor necrosis factor-α, interleukin (IL)-17A, IL-17A/F, IL-17 receptor, IL-12/23(p40), IL-23p19, Cytotoxic T-lymphocyte Antigen-4 (CTLA-4), Janus kinase, and phosphodiesterase-4 have been developed and are widely used in clinical practice. PsA is clinically and molecularly heterogeneous, and it is necessary to improve various clinical symptoms with limited treatment options simultaneously; therefore, rheumatologists sometimes encounter difficult situations in clinical practice. Hence, the development of precision medicine may improve treatment outcomes. Recently, the strategic use of molecular-targeted drugs based on the stratification of patients with PsA by peripheral blood lymphocyte phenotyping and serum cytokine concentrations has been reported to possibly lead to a higher therapeutic response. A randomized controlled trial was initiated to verify the efficacy of this treatment strategy. However, to make precision medicine in PsA feasible, shifting from conventional clinical trials to clinical trials based on biomarker profiles and accumulating further data are necessary.

Changes in and Potential Mechanisms of Circulating IgA+CD27-Class-Switched Memory B Cells in Patients With Allergic Rhinitis.

The role of memory B cells and their subgroups in allergic rhinitis (AR) and allergen immunotherapy (AIT) remains unclear. This study aimed to investigate the characteristics of memory B cells in the circulation of patients with AR and those undergoing AIT, as well as their clinical significance. This study involved a cohort comprising 32healthy control subjects, 39 individuals diagnosed with AR, and 31 AR patients who had received AIT for over one year. Visual analog scale (VAS) scores were used for symptom assessment, and the serum concentrations of immunoglobulins and cytokines were quantified. This study evaluated alterations in the proportions of peripheral blood memory B cells and their subpopulations, plasma cells, and various T-cell subsets across the three participant groups. The proportion of IgA+CD27- class-switched memory B cells in the AR group significantly decreased compared to the control group, but significantly increased following AIT (P < 0.05). In AR patients, circulating IgA+CD27- class-switched memory B cells were significantly positively correlated with Treg cells, IL-10, and IL-4 and significantly negatively correlated with IFN-γ, total IgE, sIgE, and VAS scores (P < 0.05). After AIT, the number of circulating IgA+CD27- class-switched memory B cells in AR patients was significantly positively correlated with the number of Treg cells and IL-10 and significantly negatively correlated with the VAS score (P < 0.05). The IgA+CD27- class-switched memory cell subset in human peripheral blood may serve as a potential biomarker for evaluating AR symptoms and treatment efficacy. Its mechanism may be associated with interactions between T and B cells.

Pro-inflammatory and anti-inflammatory cytokines in neonates during the acute period of novel coronavirus infection

Background. Research results on the immune response and cytokine profile in children with the new coronavirus infection SARS-CoV-2 are contradictory and insufficient, which necessitates the need to understand the nature of the course of the disease depending on age and severity of the infection. The importance of assessing risks and predicting the consequences of a new coronavirus infection in childhood makes the study of serum concentrations of pro-inflammatory and anti-inflammatory cytokines relevant.The aim. To study the level of pro-inflammatory and anti-inflammatory cytokines in newborns during the acute period of a new coronavirus infection to determine the characteristics of the immune response and identify prognostic criteria for the course of the infectious process.Materials and methods. The article presents the results of a study of the level of pro-inflammatory, anti-inflammatory cytokines and C-reactive protein (CRP) in newborns (n = 44) hospitalized with a confirmed new coronavirus infection of varying severity. The study was conducted during the acute period of COVID-19.Results. Cytokine concentrations in the blood serum of newborns were determined by enzyme immunoassay. In newborns in the acute period of a new coronavirus infection, regardless of the severity, there is a decrease in serum concentrations of interleukin-1β, interleukin-4, interleukin-6, interleukin-8, tumor necrosis factor α, interferon (INF) γ and CRP compared with the control group. The level of INF-α in the blood serum of newborns of both the main and control groups did not have significant differences.Conclusions. The cytokine profile in newborns with the new coronavirus infection SARS-CoV-2 may be due to inhibition of the innate immune system, which requires further research in this direction and increased pediatric attention to this category of children.

Could Selected Adipokines/Cytokines Serve as Markers of Adipose Tissue Dysfunction?

Elevated levels of pro-inflammatory adipokines and cytokines increase the risk of developing metabolic disorders and diseases. The aim of this study was to conduct a comparative analysis of selected adipokines/cytokines in the blood serum of adults with obesity and normal body weight. The study also evaluated the correlation of these adipokines/cytokines with selected biochemical blood parameters. The study included 46 individuals with first- and second-degree obesity and 35 individuals with normal body weight. The participants underwent nutritional status assessments, biochemical tests, and evaluations of adipokine and cytokine concentrations in blood serum. The study found higher median CRP concentrations in women with obesity than in those with normal weight. This increase was statistically significant. The results also showed significantly higher IL-6 levels in the obesity group compared to the control group in both women and men. Resistin and MMP-2 were significantly different between women with obesity and women with normal body weight. Multiple regression results indicated that higher total fat content was significantly associated with higher serum CRP and IL-6 levels and lower adiponectin levels. Interleukin 6 was the strongest predictor of adipose tissue dysfunction in both women and men. Potential markers in women could also include resistin and MMP-2. The findings suggest that gender significantly influences the regulation of inflammatory factors.

Flow-cytometric Analysis of Reactive Oxygen Species in Blood Cells: A Potential Tool for Predicting Restenosis - Insights from a Cohort Study.

In-stent restenosis (ISR) is a recurrence of a blockage in a section of the coronary artery that has previously been treated with a stent. Molecular/biochemical pathways underlying ISR are not fully understood, but inflammation and reactive oxygen species (ROS) induced oxidative stress play a significant role in the pathogenesis of restenosis. As blood cells are highly sensitive to oxidative stress and blood is readily accessible compared to other tissues, the current study flow cytometrically investigated intracellular ROS and cytokine profile of blood cells as possible markers of restenosis. Flow cytometry is commonly used for detecting ROS and analyzing oxidative stress but so far, it has not been utilized for prediction of ISR. So, the aim of the study was to explore the potential of flow cytometric assessment of ROS levels in the blood cells as predictor of ISR. The study was carried out in a total of 60 patients who had previously undergone coronary artery stent implantation. They were categorized as Group I - Coronary stent implanted patients without restenosis (n=30) and Group II - Coronary stent implanted patients with restenosis (n=30). Sociodemographics, biochemical and angiographic characteristics were assessed. Intracellular ROS and cytokine estimation in blood cells was done by using flow cytometric analysis. Flow cytometric measurements demonstrated a 1.3-fold increase in ROS levels in red blood cells (RBCs) and 2-fold increase in ROS levels in leucocytes in group II as compared to group I. Mean serum concentrations of pro-inflammatory cytokines: tumor necrosis factor-α (33.54 ± 6.48 vs. 20.10 ± 5.61, p <0.001***), interferon-gamma (21.76 ± 4.46 vs. 20.10 ± 5.61, p <0.001***), interleukin 6 (152.56 ± 30.67 vs. 113.95 ± 23.38, p <0.001***) were found to be higher in restenotic patients as compared to the non-restenotic patients. Correlation analysis showed that intracellular ROS levels of RBCs exhibited a significant positive correlation with late lumen loss in restenotic (r=0.71, p <0.01) as well as non-restenotic patients (r=0.59, p <0.01). Similarly, intracellular ROS levels of WBCs exhibited a significant positive correlation with late lumen loss in restenotic (r=0.72, p <0.01) as well as non-restenotic patients (r=0.61, p <0.01). This study highlights the role of increased levels of intracellular ROS in blood cells in the subsequent development of ISR, which can be detected flow cytometrically. The study suggests that intracellular ROS estimation in blood cells may serve as a potential marker for restenosis and their flow cytometric analysis may facilitate the prediction of ISR.

Guben Kechuan granule attenuates bronchial asthma by inhibiting NF-κB/STAT3 signaling pathway-mediated apoptosis.

Chronic asthma caused by allergies is a lung illness marked by airway remodeling and hyperresponsiveness. Guben Kechuan (GK) granule is a clinically proven formula for treating lung disease. It relieves cough and helps to clear phlegm, but the mechanisms underlying its treatment for asthma are not clear. We aimed to elucidate the efficacy and potential mechanisms by which GK ameliorates allergic asthma. Ultra-performance liquid chromatography (UHPLC-LTQ-Orbitrap-MS) identified the main chemical components of GK. The efficacy of GK was studied in an ovalbumin/alum (OVA)/AL(OH)3-sensitized rat model of bronchial asthma by measuring cytokine concentrations in serum and alveolar lavage samples, examining tissue pathology, and performing leukocyte counts. The mechanisms underlying its effectiveness in asthma were investigated by both transcriptomic and proteomic analyses. GK relieved asthma-induced airway inflammation and remodeling, reduced inflammatory cell infiltration, and decreased the levels of the inflammatory cytokines TNF-α, IL-4, IL-5, IL-6, and IL-10. Analysis of the transcriptomic and proteomic results found that asthma activated the transcription factors STAT3 and NF-κB and induced oxidative-stress damage and apoptosis. GK was found to reduce Bax and caspase-3 expression, increase Bcl-2 expression, and inhibit asthma-induced apoptosis. GK downregulated the expression of the transcription factors STAT3 and NF-kB, which decreased the inflammatory response. Decreases in CAT, SOD, and GSH reduced asthma-induced oxidative-stress damage. Our findings provide evidence that GK alleviates bronchial asthma by inhibiting apoptosis and oxidative stress damage mediated by the NF-κB/STAT3 signaling pathway.

A Two-Year cohort study examining the impact of cytokines and chemokines on cognitive and psychiatric outcomes in Long-COVID-19 patients.

This study investigates the relationship between clinical, sociodemographic, and neuropsychological symptoms and serum cytokine concentrations with long-term cognitive and psychiatric outcomes in long-COVID-19 patients. We reassessed 108 adults who survived moderate to severe COVID-19 at two intervals post-discharge (T1, mean 6.9 months; T2, mean 23.5 months). Baseline sociodemographic and clinical data were collected from hospital records, while cognitive and mental health assessments included psychometric tests such as the Hospital Anxiety and Depression Scale (HADS) and Immediate and Delayed Recall Tests from the CERAD Battery. Serum cytokine levels were measured at T1. Generalized Additive Models (GAMs), Elastic Net Regression (NET), and Psychological Network Analysis (PNA) were used to analyze the data. The GAM analysis revealed significant associations between acute COVID-19 severity and Epworth Sleepiness Score with persistent anxiety symptoms at T2. For depression, both WHO severity class and Eotaxin levels were significant predictors. The Anti-inflammatory Index showed a marginally significant relationship with immediate recall, while age was marginally associated with delayed recall performance. In NET, only anxiety was significantly associated with Epworth Sleepiness Score, WHO severity class, and Proinflammatory Index. PNA did not reveal direct connections between cytokines and neuropsychological outcomes in the graphical model. However, centrality measures indicated that the Proinflammatory Index and VEGF were more central within the network, suggesting they might be important components of the overall system. This study provides insights into the complex role of cytokines and inflammation in long-COVID-19 outcomes, potentially aiding in the identification of biomarkers for diagnosis and prognosis.

Comparison of inflammatory mediator cytokine responses to inactivated virus platform COVID-19 vaccines between elderly and young adult populations.

The coronavirus disease 2019 (COVID-19) pandemic has encouraged global vaccine research, yet vaccine effectiveness in the elderly remains a concern due to immunosenescence. The aim of this study was to compare the cytokine response elicited by an inactivated virus-based COVID-19 vaccine between elderly and young adults, focusing on key cytokines involved in cellular and humoral immunity: tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-6, IL-10, and interferon-gamma (IFN-γ). A cross-sectional study was conducted in the Jakarta-Bogor region of Indonesia from January 2023 to December 2023. The study population was divided into two age cohorts: elderly (60-85 years) and younger adults (30-40 years). Blood samples were collected twice, after the first booster dose and four weeks after the second booster dose. Serum cytokine concentrations were measured using Luminex assays with microparticles conjugated to monoclonal antibodies against TNF-α, IL-2, IL-6, IL-10, and IFN-γ. Comparisons of the cytokine levels were conducted using Student's t-tests or Mann- Whitney U tests as appropriate. A total of 74 individuals were included, with 37 each in the elderly and young adult groups. The results showed significant differences in cytokine responses between the two age groups. After the first booster, the levels of IL-6 and IFN- γ were significantly higher in young adults compared to the elderly. After the second booster, the levels of IL-6 were still significantly higher in the young adult group compared to the elderly group (p = 0.001). Data indicated that after the second booster dose, the levels of TNF-α increased significantly in the young adult group only (p = 0.004), while the levels of IL-2 (p = 0.040) and IFN-γ (p = 0.006) increased in the elderly group only compared to after the first dose. IL-10 levels increased in both groups (both had p = 0.020). This study highlights that young adults had stronger pro-inflammatory responses, while the elderly relied more on IL-2 and IFN-γ for T-cell immunity, suggesting the need for vaccination strategies for the elderly to optimize immune responses.

Correlation of Cytokine Profiles with Prostate-Specific Antigen and Disease Grade in Prostate Cancer.

BACKGROUND The development and progression of prostate cancer are multistep processes involving several growth factors, hormones, and cytokines. This study aimed to measure the serum concentrations of different cytokines and determine their correlation with prostate-specific antigen (PSA) levels and disease grade in patients with prostate adenocarcinoma. MATERIAL AND METHODS This cross-sectional study was conducted from March 2023 to March 2024 at the Clinic of Oncology of the University Hospital Center in Mostar, Bosnia and Herzegovina. Altogether, 50 male patients with prostate adenocarcinoma were included, of whom 28 had no proven metastases (PC group) and 22 had metastatic disease (MPC group). Serum concentrations of total (tPSA), free (fPSA), and complexed (cPSA) PSA were determined using a chemiluminescent microparticle immunoassay, whereas serum concentrations of cytokines were measured using a flow cytometry bead-based assay. RESULTS The MPC group had higher serum tPSA, fPSA, and cPSA levels than the PC group. The PC group had significantly higher serum levels of monocyte chemotactic protein (MCP)-1 than the MPC group (P=0.008). In the PC group, serum levels of interleukin (IL)-10 significantly correlated with cPSA. In the MPC group, serum concentrations of IL-1ß, tumor necrosis factor (TNF)-alpha, and IL-23 significantly correlated with disease grade. CONCLUSIONS Our study emphasizes the importance of MCP-1 in the development of prostate cancer, while IL-10 was the only cytokine whose serum level significantly correlated with cPSA. Serum concentrations of IL-1ß, TNF-alpha, and IL-23 may serve as potential biomarkers for disease grade.

Changes in IL-6, IL-12, IL-5, IL-10 and TGF-β1 Concentration in Patients with Treatment-Resistant Schizophrenia (TRS) Following Electroconvulsive Therapy (ECT)-A Pilot Study.

Background/Objectives: Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, IL-12, IL-5, IL-10 and TGF-β1 changes (pre- and post-ECT) and the effectiveness of ECT in TRS patients. The second aim is to search for correlations between serum concentrations of the above specified cytokines and psychometric assessments of clinical schizophrenia symptoms. Methods: The cytokine concentrations were measured in eight TRS patients on psychopharmacological treatment prior to and following ECT and in 13 control subjects. Psychopathology assessment was based on the Positive and Negative Syndrome Scale (PANSS). Results: Prior to ECT, IL-10 concentration was significantly higher in TRS patients, while IL-5 was decreased in comparison to the controls. A significant concentration decrease in the pro-inflammatory cytokines IL-6 (p = 0.012), IL-12 (p = 0.049) and anti-inflammatory IL-10 (p = 0.012) post-ECT vs. pre-ECT was observed, whereas concentrations of IL-5 and TGF-β1 did not significantly change. Also, a significant decrease in schizophrenia symptoms measured by the PANSS post-ECT was found. Furthermore, the pattern of correlations between PANSS scores and cytokine concentrations was different when comparing levels pre- and post-ECT. Additionally, correlations between changes in PANSS scores and cytokine concentrations were found. Conclusions: These results may indicate the probable impact of electroconvulsive therapy on the balance between pro- and anti-inflammatory cytokines, which may correspond to a neurobiological therapeutic effect of ECT in TRS patients.

Comparison of inflammatory mediator cytokine responses to inactivated virus platform COVID-19 vaccines between elderly and young adult populations

The coronavirus disease 2019 (COVID-19) pandemic has encouraged global vaccine research, yet vaccine effectiveness in the elderly remains a concern due to immunosenescence. The aim of this study was to compare the cytokine response elicited by an inactivated virus-based COVID-19 vaccine between elderly and young adults, focusing on key cytokines involved in cellular and humoral immunity: tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-6, IL-10, and interferon-gamma (IFN-γ). A cross-sectional study was conducted in the Jakarta-Bogor region of Indonesia from January 2023 to December 2023. The study population was divided into two age cohorts: elderly (60−85 years) and younger adults (30−40 years). Blood samples were collected twice, after the first booster dose and four weeks after the second booster dose. Serum cytokine concentrations were measured using Luminex assays with microparticles conjugated to monoclonal antibodies against TNF-α, IL-2, IL-6, IL-10, and IFN-γ. Comparisons of the cytokine levels were conducted using Student’s t-tests or Mann-Whitney U tests as appropriate. A total of 74 individuals were included, with 37 each in the elderly and young adult groups. The results showed significant differences in cytokine responses between the two age groups. After the first booster, the levels of IL-6 and IFN-γ were significantly higher in young adults compared to the elderly. After the second booster, the levels of IL-6 were still significantly higher in the young adult group compared to the elderly group (p=0.001). Data indicated that after the second booster dose, the levels of TNF-α increased significantly in the young adult group only (p=0.004), while the levels of IL-2 (p=0.040) and IFN-γ (p=0.006) increased in the elderly group only compared to after the first dose. IL-10 levels increased in both groups (both had p=0.020). This study highlights that young adults had stronger pro-inflammatory responses, while the elderly relied more on IL-2 and IFN-γ for T-cell immunity, suggesting the need for vaccination strategies for the elderly to optimize immune responses.

Exposure-biomarker analyses for cytokine release syndrome or infusion-related reaction, pain, and cytokine concentrations in serum during treatment with ubamatamab, a MUC16xCD3 bispecific antibody, among patients with recurrent ovarian cancer

Exposure-biomarker analyses for cytokine release syndrome or infusion-related reaction, pain, and cytokine concentrations in serum during treatment with ubamatamab, a MUC16xCD3 bispecific antibody, among patients with recurrent ovarian cancer

Investigating the impact of tocilizumab on serum cytokines concentrations in Japanese FMF patients: a sub-analysis of the NUH01FMF study

Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disease, characterized by recurrent fever, arthritis, rash, and serositis, and is caused by mutations in the MEFV gene coding for the pyrin protein. The primary treatment goal is to prevent acute attacks and minimize subclinical inflammation to avoid secondary amyloidosis with colchicine as the first-line treatment. However, 10-20% of patients are colchicine-resistant or intolerant. While the therapeutic potential of IL-6 inhibitors such as tocilizumab (TCZ) has been suggested, the detailed serum cytokine profiles after TCZ treatment in patients with FMF remain largely unexplored. This study focused on a sub-analysis of a clinical trial evaluating TCZ in patients with colchicine-resistant FMF (crFMF). We analyzed the serum cytokine profiles at 0, 2, 4, 8, 12, 16, 20, and 24 weeks in the TCZ and placebo groups. Our findings revealed a decrease in serum C-X-C motif chemokine ligand 1 and vascular endothelial growth factor levels in the TCZ group at week 4 compared to baseline, which persisted until week 24, indicating the potential of TCZ to manage crFMF by modulating specific inflammatory cytokines. Further research is required to confirm these findings and optimize the treatment strategies for FMF.