Blood Cytokine Levels Research Articles

Analysis of the Blood Levels of NK and NKT Cells in Patients with Severe SARS-CoV-2 Infection.

Clinical features of SARS-CoV-2 infection vary, ranging from asymptomatic cases to pneumonia, and other serious complications. Some populations have been observed to be at higher risk for severe disease and death compared to other ethnical groups. To evaluate two parameters of the innate immune system, that play a significant role in viral immunity. In samples of peripheral blood from sixteen patients with severe COVID-19, ten with asymptomatic to mild illness, and fifteen healthy subjects, the percentage of NK and NKT cells, the expression of different NK cell receptors and the blood levels of pro-inflammatory cytokines were tested. We observed that patients with severe COVID-19 showed significantly lower frequencies of both CD56dim and CD56bright NK cells compared to patients with mild illness or healthy controls. Furthermore, patients with severe manifestation of COVID-19 exhibited an aberrant expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46. Similarly, NK cells from these patients showed statistically significant differences in the expression of various killer immunoglobulin-like receptors (KIRs) in the two main cell subsets (CD56bright, CD56dim) compared to controls or patients with mild disease. Moreover, patients with severe illness displayed decreased frequency of NKT cells (defined as CD3+CD56+) and elevated blood levels of the cytokines IL-6 and IL-8. This study suggests that the abnormal features of NK and NKT cells observed in patients with severe SARS-CoV-2 infection may play an important role in the outcome of this infectious disease in various population groups.

374 Expression of ORAI1 and STIM1 genes and levels of cytokines in blood in HIV patients with HIV- associated skin pathologies and in a control group in Latvia

374 Expression of ORAI1 and STIM1 genes and levels of cytokines in blood in HIV patients with HIV- associated skin pathologies and in a control group in Latvia

Secukinumab (Anti-IL-17A Therapeutic Antibody) Improves Clinical Outcome for a Mixed Endotype CRS.

We identified two CRSwNP patients who had previously failed treatment with an anti-IL-4/IL-13 antibody (dupilumab). Based on their clinical characteristics and blood cytokine levels, we considered them mixed Type II/Type III cases and treated them with an anti-IL-17 antibody (secukinumab). Anti-IL-17 antibody secukinumab was superior in reducing their NPS and SNOT-22 values compared to dupilumab. IL-17 could be a promising target for non-type II and mixed endotype CRS treatment.

Bactericidal effect of far ultraviolet-C irradiation at 222 nm against bacterial peritonitis.

Far ultraviolet-C irradiation at 222 nm has potent bactericidal effects against severe infections such as peritonitis, with minimal cytotoxicity. Bacterial peritonitis due to bowel perforation is a serious condition with high mortality despite current treatments. This study investigated the safety and efficacy of intraperitoneal far ultraviolet-C irradiation at 222 nm. In vitro experiments optimized the fluid conditions for bacterial or protein concentrations prior to in vivo evaluation. In vivo efficacy was assessed in a rat peritonitis model induced by Escherichia coli, measuring intra-abdominal bacterial concentration, blood cytokine levels, and mortality rates. Safety was evaluated by analyzing cyclobutane pyrimidine dimers as markers of DNA damage in five abdominal organs: stomach, small intestine, colon, liver, and spleen. Statistical analyses employed parametric methods for normally distributed data and non-parametric methods for data without normality. Optimal in vitro conditions included 106 CFU/mL bacteria, 0.5 mW/cm2 irradiation, and 10-3 mg/mL protein. In the rat model, far ultraviolet-C irradiation at 222 nm significantly decreased intra-abdominal bacteria, reduced blood cytokines (interleukin-1β and interleukin-6), and elevated survival rates from 20% to 60%, compared to lavage alone. The formation of cyclobutane pyrimidine dimers was significantly lower with 222 nm irradiation than with 254 nm, suggesting reduced DNA damage. These findings indicate that far ultraviolet-C irradiation at 222 nm, when combined with lavage, represents a promising therapeutic strategy for bacterial peritonitis, providing effective bacterial reduction and a favorable safety profile. Further research is needed to verify these findings and investigate long-term safety and potential clinical applications.

Clinical and etiological characteristics and cytokine profile in school-age children with community-acquired pneumonia

The urgent task of modern pediatrics is the study of the etiology and pathophysiology of community-acquired pneumonia in school-aged children due to difficulties in diagnosis and treatment, as well as the high risk of life-threatening complications and death.Purpose. To investigate the activity of pro-inflammatory and anti-inflammatory responses as measured by cytokine levels in the peripheral blood of children with community-acquired pneumococcal and non-pneumococcal pneumonia.Material and methods. The etiology of community-acquired pneumonia was confirmed by comparing the results of rapid testing of pneumococcus in urine and data from traditional bacteriological methods. The study included 118 children (57 boys and 61 girls) aged 7 to 16 years with various morphological variants of community-acquired pneumonia, which were divided into 2 groups. The first group included 28 children with pneumococcal etiology of community-acquired pneumonia, and the second group included 90 patients with non-pneumococcal community-acquired pneumonia. Levels of interleukins IL-1, IL-4, IL-8 and TNF-α were determined in all children by enzyme immunoassays.Results. In the etiology of community-acquired pneumonia in school-age children, atypical pathogens are responsible for more than 50% of cases. The clinical effectiveness of rapid testing of pneumococcal antigens in urine has been shown, and their use in routine pediatric practice has made it possible to timely identify a group of severe community-acquired pneumonia and reasonably prescribe antibacterial medications. It has been demonstrated that pneumococcal-induced pneumonia is characterized by higher levels of proinflammatory cytokines. These levels, along with the clinical course of the disease, confirm the high level of systemic inflammation. Relatively lower levels of proinflammatory cytokines corresponded to a more mild clinical picture of community-acquired pneumonia of non-pneumococcal etiology, which on the one hand may reflect a relatively «balanced» inflammatory response, and on the other hand determine the protracted and polyclinic course of the infectious process.Conclusion. The etiology of community-acquired pneumonia in school-age children is dominated by atypical pathogens. Community-acquired pneumonia of pneumococcal etiology has more severe clinical courses, and their early identification will allow for the appropriate prescription of initial antibacterial treatment.

Dual role of ramR mutation in enhancing immune activation and elevating eravacycline resistance in Klebsiella pneumoniae

AbstractThe rise of Klebsiella pneumoniae resistant to last‐resort antimicrobials poses an urgent threat to global health. The ramR‐ramA regulatory system critically influences drug resistance by regulating the AcrAB‐TolC efflux pump, which also plays a crucial role in the pathogenicity of K. pneumoniae. However, the mechanism of the ramR‐ramA system on bacteria‐host interaction remains unclear. To determine how specific mutations in ramR influence eravacycline (ERV) resistance and their impact on the immune activation capabilities of K. pneumoniae, thereby highlighting potential targets for therapeutic intervention, we performed genetic sequencing to identify mutations in ramR. Then, the CRISPR‐Cas9 technology was employed to construct specific ramR mutations into K. pneumoniae, which were then subjected to phenotypic and functional assays in both in vitro and in vivo (mouse models, macrophage, and blood‐killing experiment) settings. ramR L58P and F165L genetic alterations disrupt the binding affinity of RamR to the ramA promoter, thereby upregulating the efflux pump expression and increasing ERV minimum inhibitory concentration values up to 64‐fold compared to the wild‐type. Concurrently, these mutations modulate lipid A structure by increasing 2‐hydroxy fatty acid chain abundance. In mouse models, ramR L58P and F165L mutants showed lower bacterial burden in organs (spleen, lung, and kidney) 6 h post‐infection, and are fast cleared in 48 h. Furthermore, despite lower intracellular bacterial loads, ramR L58P and F165L mutants induce heightened pro‐inflammatory cytokine responses in macrophages and elevate systemic cytokine levels (interleukin [IL]2, IL4, IL6, IL12, interferon‐α, and interferon‐γ) in human blood co‐culture experiments. This study illuminates the critical role of ramR mutations in conferring ERV resistance and enhancing immune responses in K. pneumoniae. The dual impact of these mutations on both antimicrobial resistance and immune activation not only underscores the challenges in treating infections but also advocates for heightened surveillance and innovative strategies to counteract the emerging threat of antimicrobial‐resistant K. pneumoniae.

Wire injury induced moderate aortic valve stenosis in mice is accompanied by a chronic systemic inflammatory reaction

Abstract Background Patients with aortic valve stenosis (AS) have elevated serum levels of inflammation markers, and blood cytokine levels correlate with ventricular recovery after transcatheter aortic valve replacement. While presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon AS has been performed, yet. Purpose Hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods AS was induced by wire injury (WI) or sham surgery was performed in 3-4 months old male C57Bl/6J mice. AS severity, left ventricular (LV) function and hypertrophy indices were assessed with echocardiography (echo). After four weeks, explanted organs were weighted, and flow cytometry identified total leukocyte numbers in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes) and uptake of Cy5-labelled perfluorocarbon nanoemulsions by whole blood leukocytes. Costimulatory molecules (flow cytometry, RT-qPCR) and cytokines (RT-qPCR, Multiplex Immunoassay) were analysed in heart, peripheral immune organs and blood. Results R-values were positive for spleen weight correlation with AS severity, cardiac function and mass suggesting cardiac hypertrophy to preserve heart function. Myocardial myeloid and T cell r-values were positive or negative, respectively, for correlation with spleen and liver weight, hinting at T cell recruitment from peripheral stores. Immune cell numbers in peripheral lymph nodes and spleen showed negative r-values for correlation with heart hypertrophy indices; number of liver myeloid cells correlated negatively with LV wall thickness (monocytes=-0.8571, p=0.0238) suggesting immune cell recruitment to hypertrophic hearts. Cytokine mRNA levels trended mainly towards increase in heart and regional lymph nodes and reduction in spleen and liver after WI. Correlation with echo was more homogeneous after WI, with r-values mainly positive, except of T cell activation markers, for aortic valves, but negative for myocardium, hinting at mechanisms preserving heart function. Correlating unchanged cytokine protein levels in myocardium and plasma with echo, r-values were mostly positive for myocardium, and were more positive than in sham for plasma. Echo and costimulatory molecule correlation showed a more homogeneous pattern in WI, with mostly positive r-values in myocardium and periphery, while most r-values were negative in sham. Together with reduced PFC-uptake by lymphatic cells, this hints at systemic immune cell activation in AS. Conclusion The results suggest that number and activation state of leukocytes in peripheral organs are directly linked to cardiac processes in AS. Considering the pathological value of inflammation, it is crucial to in future studies find out if modulation of the systemic inflammatory reaction relieves severity of AS and prevents development of heart failure.

Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.

Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice. Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP. Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%). FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.

Immunomodulatory Effects of a Prebiotic Formula with 2'-Fucosyllactose and Galacto- and Fructo-Oligosaccharides on Cyclophosphamide (CTX)-Induced Immunosuppressed BALB/c Mice via the Gut-Immune Axis.

Obejectives: This study explored the immunomodulatory effects of a prebiotic formula consisting of 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOSs), and fructo-oligosaccharides (FOSs) (hereinafter referred to as 2FGF) in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice and its underlying mechanisms. Methods: Sixty healthy female BALB/c mice were randomly divided into the following groups: normal control (NC) group; CTX treatment (CTX) group; 2FGF low-dose (2FGF-L) group; 2FGF medium-dose (2FGF-M) group; and 2FGF high-dose (2FGF-H) group. An immunosuppressed model was established in the 2FGF-H group by intraperitoneal injection of 80 mg/kg CTX. After 30 days of 2FGF intervention, peripheral blood, spleen tissue, thymus tissue, and intestinal tissue from the mice were collected and analyzed. The changes in weight and food intake of the mice were recorded weekly. Hematoxylin-eosin (HE) staining was used to observe the histological change of the spleen tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect cytokine levels in peripheral blood. Flow cytometry was used to analyze T lymphocyte subgroup ratio of splenic lymphocytes. Western blot analysis was conducted on intestinal tissues to assess the expression of proteins involved in the tight junction, toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. Additionally, molecular techniques were used to analyze the intestinal microbiota. Results: The results showed that 2FGF restored CTX-induced splenic injury, increased the number of splenic T lymphocytes, and elevated serum cytokines such as interleukin-4 (IL-4) and IL-10. In the intestine, 2FGF upregulated the expression of intestinal epithelial tight junction proteins such as Claudin-1 and zonula occludens 1 (ZO-1), thereby enhancing intestinal barrier function and activating the MAPK and NF-κB pathways via TLR4. Furthermore, 2FGF elevated the α-diversity (Shannon and Simpson indices) of the gut microbiota in CTX-induced immunosuppressed mice, enriching bacteria species positively correlated with anti-inflammatory cytokines (e.g., IL-4) such as g_Streptomyces and g_Bacillus and negatively correlated with pro-inflammatory cytokines (e.g., IL-1β) such as g_Saccharomyces. The results suggest that 2FGF may enhance immunity via the gut-immune axis. Conclusions: The 2FGF prebiotic formula showed an immunomodulatory effect in CTX-induced immunosuppressed mice, and the mechanism of which might involve optimizing the gut flora, enhancing intestinal homeostasis, strengthening the intestinal barrier, and promoting the expression of immune factors by regulating the TLR-4/MAPK/NF-κB pathway.

The Streptococcus agalactiae LytSR two-component regulatory system promotes vaginal colonization and virulence in vivo.

Streptococcus agalactiae (or group B Streptococcus, GBS) is a leading cause of neonatal sepsis and meningitis globally. To sense and respond to variations in its environment, GBS possesses multiple two-component regulatory systems (TCSs), such as LytSR. Here, we aimed to investigate the role of LytSR in GBS pathogenicity. We generated an isogenic lytS knockout mutant in a clinical GBS isolate and used a combination of phenotypic in vitro assays and in vivo murine models to investigate the contribution of lytS to the colonization and invasive properties of GBS. Deletion of the lytS gene in the GBS chromosome resulted in significantly higher survival rates in mice during sepsis, accompanied by reduced bacterial loads in blood, lung, spleen, kidney, and brain tissues compared to infection with the wild-type strain. In a mouse model of GBS vaginal colonization, we also observed that the lytS knockout mutant was cleared more readily from the vaginal tract compared to its wild-type counterpart. Interestingly, lower levels of proinflammatory cytokines were found in the serum of mice infected with the lytS mutant. Our results demonstrate that the LytSR TCS plays a key role in GBS tissue invasion and pathogenesis, and persistence of mucosal colonization.IMPORTANCEStreptococcus agalactiae (group B Streptococcus, or GBS) is a common commensal of the female urogenital tract and one of WHO's priority pathogens. The bacterium has evolved mechanisms to adapt and survive in its host, many of which are regulated via two-component signal transduction systems (TCSs); however, the exact contributions of TCSs toward GBS pathogenicity remain largely obscure. We have constructed a TCS lytS-deficient mutant in a CC-17 hypervirulent GBS clinical isolate. Using murine models, we showed that LytSR regulatory system is essential for vaginal colonization via promoting biofilm production. We also observed that lytS deficiency led to significantly attenuated virulence properties and lower levels of proinflammatory cytokines in blood. Our findings are of significant importance in that they unveil a previously unreported role for LytSR in GBS and pave the way toward a better understanding of its ability to transition from an innocuous commensal to a deadly pathogen.

Effects of Dietary Yeast β-1,3/1,6-D-Glucan on Immunomodulation in RAW 264.7 Cells and Methotrexate-Treated Rat Models.

A new subclass of nutraceuticals, called immunoceuticals, is dedicated to immunological regulation. Although yeast-derived β-1,3/1,6-D-glucan shows promise as an immunoceutical candidate, further studies are needed to define its precise immune-enhancing processes and to standardize its use. Following methotrexate (MTX)-induced immunosuppression in rats, we evaluated the immunomodulatory efficacy of a highly pure and standardized β-1,3/1,6-D-glucan sample (YBG) in RAW 264.7 macrophages. In in vitro and in vivo models, YBG demonstrated remarkable immunomodulatory effects, such as repair of immune organ damage, elevation of blood cytokine levels, and enhanced phagocytosis and nitric oxide production in RAW 264.7 cells. These results are consistent with the established immunostimulatory properties of β-glucan. It is noteworthy that this research indicates the potential of YBG as an immunomodulatory nutraceutical, as it is among the first to demonstrate immunological augmentation in an immunosuppression setting produced by MTX. Based on these observations, further investigation of YBG is warranted, particularly given its potential to emerge as a combination immunoceutical to mitigate immunosuppression and reduce the risk of infection in rheumatoid arthritis (RA) patients receiving long-term MTX therapy.

Locomotor and gait changes in the LPS model of neuroinflammation are correlated with inflammatory cytokines in blood and brain.

Lipopolysaccharide (LPS) challenge in mice has been used to identify the mechanisms and therapeutics for neuroinflammation. In this study, we aimed to comprehensively evaluate the behavioral changes including locomotion, exploration, and memory, correlating them with a panel of thirteen inflammatory cytokines in both blood and brain.We found that acute LPS administration (0.83 mg/Kg i.p.) reduced body weight, food intake, and glucose levels compared to the saline-injected mice, concomitant with decreased activity in home cage monitoring. Locomotion was significantly reduced in Open Field, Introduced Object, and Y-Maze tests. Decreased exploratory behavior in the Y-Maze and Introduced Object tests was noticed, by measuring the number of arms explored and object interaction time, respectively. Additionally, in rotarod, LPS administration led to a significant decrease in the distance achieved, while in the MouseWalker, LPS led to a reduction in average velocity.LPS induced a decrease in microglia ramification index in the motor cortex and the striatum, while surprisingly a reduction in microglia number was observed in the motor cortex.The concentrations of thirteen cytokines in the blood were significantly altered, while only CXCL1, CCL22, CCL17, G-CSF, and IL-12p40 were changed in the brain. Correlations between cytokine levels in blood and brain were found, most notably for CCL17 and CCL22. TGFβ was the only one with negative correlations to other cytokines. Correlations between cytokines and behavior changes were also disclosed, especially for CCL17, CCL22, G-CSF, and IL-6 and negatively for TGFβ and IL-10.In summary, our study employing acute LPS challenge in mice has revealed a comprehensive profile of behavioral alterations alongside significant changes in inflammatory cytokine levels, both in peripheral blood and brain tissue. These findings contribute to a deeper understanding of the interplay between inflammation and behavior, with possible implications for identifying prognostics and therapeutic targets for neuroinflammatory conditions.

Correlations between Metabolic Parameters, Blood Cytokine Levels, and Behavioral Parameters in Male and Female Rats of Different Age after Intrauterine Stress.

We studied interrelationships between behavioral parameters, metabolic processes, and cytokine content in the blood of male and female rats at different stages of postnatal ontogeny after intrauterine stress (mothers were forced to swim in cold water from the 10th to the 16th day of pregnancy). Correlations between behavioral and metabolic parameters in prenatally stressed rats were revealed at an earlier age (day 21 of life) than in controls. In comparison with intact rats, in males exposed to intrauterine stress no relationships between these parameters were revealed at older age, while in females, their direction and character change on day 60 of life. In prenatally stressed males, correlations of the blood levels of IL-6 were revealed: inverse relationships with behavioral parameters on the days 21 and 30 and direct relationships with metabolic parameters on day 60 of life. In prenatally stressed females on day 30 of life, we observed negative correlations between IL-4 levels and metabolic parameters that were absent under normal conditions. Thus, intrauterine stress leads to reorganization of the relationships between the parameters of metabolic and immune processes, which are essential for the purposeful behavior of mammals. The effects of stress seem to depend on the sex of the offspring and stage of postnatal development.

Blood markers for type-1, -2, and -3 inflammation are associated with severity of acutely decompensated cirrhosis

In patients with acutely decompensated cirrhosis (ADC) who present with clinically apparent precipitants (i.e., infections, acute liver injury), alterations in blood markers of inflammation associate with progression toward severe phenotypes (e.g., acute-on-chronic liver failure, ACLF). It is unclear whether alterations in blood inflammatory markers may associate with progression of ADC independently of precipitants. We prospectively enrolled 394 patients admitted for ADC who were classified into four phenotypes of increasing severity: no organ dysfunction (n=168), organ dysfunction alone (n=72), organ failure without ACLF (n=91), and ACLF (n=63). Clinical blood cell counts and serum levels of inflammatory markers (including soluble markers related to type-1, type-2, and type-3 inflammation) were obtained at enrollment. Ordinal regression with adjacent categories logit model adjusted for confounders (including precipitants) was used to analyze associations between changes in each blood inflammatory marker and the worsening of ADC. Inflammatory markers that were associated with higher risk of progressing to the next more severe stage were as follows: increasing neutrophil counts (adjusted common odds ratio [cOR] 1.17, 95%CI 1.06-1.28); increasing levels of the type-2 cytokine interleukin (IL)-25 (cOR 1.21, 95%CI 1.06-1.39), type-3 cytokines IL-6 (cOR 1.15, 95%CI 1.02-1.28) and IL-22 (cOR 1.16, 95%CI 1.03-1.30), or anti-inflammatory soluble CD163 (cOR 1.94, 95%CI 1.58-2.38); decreasing lymphocyte counts (cOR 0.77, 95%CI 0.68-0.87), or decreasing levels of the type-1 cytokine IFN-γ (cOR 0.85, 95%CI 0.75-0.95). Among patients with ADC, alterations in blood levels of cytokines related to type-1, type-2 and type-3 inflammation, together with neutrophilia, lymphopenia and elevated anti-inflammatory signals were individually associated with an increased risk of progressing toward ACLF, independently of the presence of clinically apparent precipitants.

Correlations of gray matter volume with peripheral cytokines in Parkinson's disease

IntroductionPeripheral cytokine levels may affect specific brain volumes. Few studies have examined this possible relationship. ObjectiveIn a case–control study, we used magnetic resonance imaging (MRI) voxel-based morphological analysis techniques to examine the relationship between gray matter volume changes and cognitive, motor and emotional dysfunction as well as between gray matter volume changes and peripheral blood cytokine levels. MethodA total of 134 subjects, comprising 66 PD patients and 68 healthy controls, were recruited. Peripheral venous blood was collected to measure the concentrations of 12 cytokines, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-α, IFN-γ, and TNF-α. All the subjects also underwent MRI, where 3D-T1-weighted MR images were used for the analysis. In addition, the Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE), Unified Parkinson's disease Rating Scale (UPDRS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were assessed in PD patients. Statistical parameter mapping 12 software was used for the statistical analysis of the images. ResultCompared with control patients, PD patients presented decreased gray matter volume (GMV) in the bilateral frontal lobe, temporal lobe, parietal lobe, occipital lobe, insula, and right cerebellar lobule VIII. Regional GMV in the temporal lobe, parietal lobe, and cerebellum was correlated with MoCA, MMSE, UPDRS, HAMA, and HAMD scores in PDs. In addition, the regional GMV in PDs was correlated with the concentrations of cytokines, including IL-4, IL-6, IFN-γ, and TNF-α. The IL-6 concentration was negatively correlated with the UPDRS-IV score. ConclusionPD patients exhibit gray matter atrophy in a wide range of brain regions, which are symmetrically distributed and mainly concentrated in the frontal and temporal lobes, and these changes may be linked to motor disorders and neuropsychiatric manifestations. Cytokine concentrations in peripheral blood are correlated with regional gray matter volume in PDs, and the IL-6 level affects gray matter volume in the left precentral gyrus and the manifestation of motor complications.

Sex-Specific Cytokine, Chemokine, and Growth Factor Signatures in T1D Patients and Progressors.

While studies have reported altered levels of cytokines in type 1 diabetes (T1D) patients, the results are inconsistent, likely because of variable factors. This study tests the hypothesis that there are sex-based differences in cytokine levels in T1D, prior to and after disease onset. We analyzed 48 blood cytokine, chemokine, and growth factor levels using a multiplex assay. We found only two cytokines, M-CSF and IL-6, with significant differences between T1D patients (n=25) versus controls overall (n=25). However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Inflammatory cytokines (TNF-α, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (MIP-1α, RANTES, MIP-3) were lower in female T1D patients compared to female controls, but not in males. IL-22 was lower in female T1D patients compared to female controls, while it was higher in male T1D patients compared to male controls. In contrast, growth factors (EGF, PDGF-AB/BB) were higher in male T1D patients compared to male controls. In T1D progressors (children who developed the disease years after the sample collection, n=16-21), GROa was lower compared to controls in both sexes. Our findings underscore the importance of understanding sex-specific differences in T1D pathogenesis and their implications for developing personalized treatments.

Effect of photodynamic therapy on peripheral immune system for unresectable cholangiocarcinoma

BackgroundPhotodynamic therapy (PDT) has been emerging as a promising treatment for unresectable cholangiocarcinoma (CCA). A number of experiments have demonstrated that PDT could enhance antitumor immunity significantly. However, the impact of PDT on peripheral immune system for unresectable CCA remains unclear. MethodsIn a clinical trial comparing the perioperative and long-term outcomes of PDT+stent treatment and stent alone treatment for unresectable CCA, we tested the levels of lymphocytes (CD4+ T cells, CD8+ T cells, NK cells, B cells and Treg cells) and immune-related cytokines (IL-4, IL-6, IL-10, TNF-α, TGF-β, perforin, GM-CSF and IFN-γ) in peripheral blood before and after PDT+stent treatment or stent alone treatment and analyzed the influence of PDT on peripheral immune system for unresectable CCA. ResultsBefore treatment, the levels of all the immune cells and immune-related cytokines did not show significant differences between the PDT+stent group and stent alone group. The ratio of CD8+ T cells increased significantly after PDT treatment, but other kinds of lymphocytes did not show significant difference. Increased level of IL-6 and decreased level of perforin and TGF-β after PDT treatment were demonstrated, whereas no significant changes were found for other immune-related cytokines. ConclusionPDT altered the levels of immune cells and immune-related cytokines in the peripheral blood of unresectable CCA patients, potentially correlating with the therapeutic efficacy of PDT in unresectable CCA treatment. Future studies could delve deeper into this aspect to explore how PDT can be more effectively utilized in the management of unresectable CCA.

Longitudinal analysis at pre- and post-flare of T peripheral helper and T follicular helper subsets in patients with systemic lupus erythematosus

ObjectiveWe focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare. MethodsThis study included inactive (n = 29) and active (n = 55) patients with SLE. Tph subsets, Tfh subsets, CD11chi B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array. ResultsActive SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare. ConclusionIncreased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.

Cfhr1 gene deficiency exacerbates Staphylococcus aureus-induced sepsis and acute lung injury through complement alternative pathway hyperactivation

ObjectiveTo explore the role of excessive activation of the complement alternative pathway (AP) in acute lung injury (ALI) and sepsis induced by Staphylococcus aureus. Subsequently, we aimed to define the effects of Cfhr gene deletion on Factor H expression, AP activation, and the development of sepsis-induced ALI. MethodsA sepsis-induced ALI model was established in Cfhr1-knockout mice by tail vein injection of S. aureus. Sepsis scores, bacterial load in lungs, and cytokine and complement factor levels in blood and lung tissues were evaluated at 6, 12, and 24 h after model establishment. Real-time quantitative PCR and RNA sequencing (RNA-seq) were employed to assess the expression of complement pathway-associated molecules and identify differentially expressed genes (DEGs) related to immune responses. ResultsCompared to wild-type mice, Cfhr1-knockout mice exhibited significantly increased C3a formation in lung tissues following S. aureus infection, indicating enhanced terminal complement pathway activation. Notably, these mice also had higher bacterial colony counts in the lungs, suggesting impaired S. aureus clearance. Transcriptome analysis provided further insights into the impact of Cfhr1 deletion on biological processes and signalling pathways involved in immune response regulation. ConclusionCfhr1 deletion leads to excessive AP activation, exacerbating S. aureus-induced sepsis and ALI.

Efficacy of budesonide/formoterol inhalation powder in treating viral pneumonia in children.

Respiratory viruses are increasingly detected in children with community-acquired pneumonia. Further strategies to limit antibiotic use in children with viral pneumonia are warranted. To explore clinical efficacy of budesonide/formoterol inhalation powder for viral pneumonia in children and its impact on cellular immunity and inflammatory factor production. A total of 60 children with viral pneumonia were recruited: 30 receiving budesonide/formoterol inhalation powder and 30 conventional symptomatic treatment. Outcome measures included peripheral blood levels of inflammatory cytokines, CD4+, CD8+, Th1, Th2, Th17 and Treg, clinical efficacy, and incidence of adverse reactions. Compared with the control group, the observation group showed a significant reduction in interleukin-6 and high-sensitivity C-reactive protein levels after treatment. Compared with the control group, the observation group showed a significant increase in CD4+/CD8+ and Th1/Th2 levels, and a decrease in Th17/Treg levels after treatment. The total effective rates in the observation group and the control group were 93.75% and 85.00%, respectively, which was a significant difference (P = 0.003). Budesonide/formoterol inhalation powder significantly improved therapeutic efficacy for viral pneumonia in children. The mechanism of action may be related to downregulation of the inflammatory response and improved cellular immune function.