Serum IL-6 Levels Research Articles

Systemic profile of pro-inflammatory and anti-inflammatory cytokines and its changes in patients with cataract after surgery

Background. Due to its high prevalence and morbidity, cataract is an urgent medical and social problem. In recent years, immune inflammation, in particular the immune regulation of dystrophic processes, has been of great importance in the pathogenesis of eye diseases. Immunological disorders play a crucial role in the development of age-related eye diseases (cataract, corneal dystrophy, glaucoma, age-related macular degeneration). The effect of pro-inflammatory and anti-inflammatory cytokines on the development of age-related cataract remains understudied, as well at their role in predicting the course of the postoperative period after extraction of age-related cataract has not been fully stu­died, which determines the relevance of the study. The objective: to assess the state of cytokine profile in patients with age-related cataract by determining the content of pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) interleukins in blood serum before and after surgical treatment of cataract. Materials and methods. The level of pro-inflammatory (IL-1β, IL-6) and anti-inflammatory cytokines (IL-4, IL-10) was studied before and after surgical treatment in 28 patients with age-related cataract (56 eyes), 8 men and 20 women aged 42 to 82 years. The average age of the patients was 71.79 ± 1.90 years. Serum content of cytokines was determined by the enzyme-linked immunosorbent assay using test systems Vector-Best-Ukraine. Results. There was no excess of IL-1β and IL-6 reference values in the blood serum of patients with age-related cataract prior to surgical treatment. Analysis of the pro-inflammatory IL-6 in these patients depending on sex revealed a significant increase in its level by 1.3 times in men and a significant decrease by 1.1 times in women compared to its average content (p < 0.06 and p < 0.01, respectively). The level of anti-inflammatory IL-4 and IL-10 in the blood serum of the examined patients was within the reference values. When studying the content of pro-inflammatory and anti-inflammatory interleukins in serum depending on sex and age in patients with age-related cataract aged 75 years and older, there was a statistically significant increase in IL-6 and IL-10. In this age group, the level of IL-6 was 1.4 times higher in men compared to women, and IL-10 was 1.8 times higher in women than in men. In patients with age-related cataract after surgical treatment, serum content of pro-inflammatory IL-1β, IL-6 and anti-inflammatory IL-4, IL-10 was higher than levels before surgery. The highest levels of IL-1β, IL-6 were in patients with postoperative corneal edema. Serum content of IL-6 in patients with postoperative corneal edema was higher compared to that of IL-1β. Levels of IL-4, IL-10 were higher in patients with postoperative corneal edema, IL-10 in these patients prevailed over IL-4. Conclusions. In patients with age-rela­ted cataract, the content of pro-inflammatory and anti-inflammatory cytokines in the blood serum corresponds to reference values and has no signi­ficant differences from the control group. However, determination of the cytokine profile in people with age-related cataract revealed a violation of the systemic immunological status depending on age and gender. According to our results, patients with age-related cataract over 75 years of age had a significant increase in the level of pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 in blood serum. In this age group, IL-6 was higher in men and IL-10 was higher in women. We also noted the absence of significant differences in the content of IL-1β, which may indicate a more specific value of IL-6 levels for the development of cataract. In patients with age-related cataract after surgical treatment, serum levels of pro-inflammatory IL-1β, IL-6 and anti-inflammatory IL-4, IL-10 were higher than preoperative ones. The highest levels of IL-1β, IL-6 were in the blood serum of patients with postope­rative corneal edema, and a decrease in the level of IL-4, IL-10 was also noted in cases of corneal edema. Serum content of IL-6 in patients with postoperative corneal edema was higher than that of IL-1β, and IL-10 prevailed over IL-4 levels.

Preliminary evaluation of the protective effect of rEi-SAG19 on Eimeria intestinalis infection in rabbits

Eimeria intestinalis is one of the most pathogenic coccidia species in rabbits. Anticoccidial treaments are the main measures to control rabbit coccidiosis now, but there are drug resistance and residues concerns. Therefore, vaccine has been used as an alternative strategy. The surface antigens (SAGs) of apicomplexan protozoa play a role in adhesion and invasion of host intestinal cells, and are considered to be potential candidate antigens for vaccines. In this study, transcriptional analysis of 5 Ei-SAGs genes at four developmental stages was conducted, then the Ei-SAG19 gene were screened out for prokaryotic expression and the reactogenicity of recombinant SAG19 (rEi-SAG19) was investigated by immunoblotting. To assessment the protective effects of rEi-SAG19, rabbits (n = 40) were randomly divided into four groups (Blank control, PBS-infected, Trx-His-S-Quil-A-infected and rEi-SAG19 immunized groups), the rEi-SAG19 immunized group was subcutaneously immunized with 100 μg rEi-SAG19 in the neck with an interval of two weeks, and challenged with 5×104 homologous oocysts two weeks after the second immunization. Two weeks after the challenge, all rabbits were sacrificed. After that, the level of serum specific IgG antibody was detected weekly and the level of cytokines in serum before the challenge were determined. At the end of the experiment, the weight gain, oocyst reduction rate, lesion score and anticoccidial index (ACI) were calculated. The results showed that rEi-SAG19 has a good reactogenicity. The relative weight gain rate, oocyst reduction rate and ACI of the rabbits in rEi-SAG19 immunized group were 80.51%, 72.6%, and 165.1, respectively, which has a moderate protective effect. The level of serum specific IgG antibody and IL-4 rised significantly (P < 0.05), but the levels of IL-2, IFN-γ and IL-10 had no significant difference (P > 0.05). Our results indicated that rEi-SAG19 could provides moderate protective effect against E. intestinalis infection in rabbits (ACI = 165.1). Therefore, rEi-SAG19 could be used as a vaccine candidate antigen for E. intestinalis.

Novel TSPO Ligand 2-Cl-MGV-1 Can Counteract Lipopolysaccharide Induced Inflammatory Response in Murine RAW264.7 Macrophage Cell Line and Lung Models.

We assessed the anti-inflammatory activity of the TSPO ligand 2-Cl-MGV-1. Lipopolysaccharide (LPS) was used to induce inflammatory response in a murine RAW264.7 macrophage model (LPS: 100 ng/mL) and a mouse model (C57BL/6) of lung inflammation (LPS: 5 mg/kg). In the macrophage model, the presence of 2-Cl-MGV-1 (25 µM) caused the LPS-induced elevation in nitrite levels to decrease by 70% (p < 0.0001) and interleukin (IL)-6 by 50% (p < 0.05). In the mouse model, 2-Cl-MGV-1, administered 30 min before, or co-administered with, an LPS injection, significantly inhibited the elevation in serum IL-5 levels (both by 65%; p < 0.001 and p < 0.01, respectively). 2-Cl-MGV-1 administration to mice 30 min before LPS injection and 1 h thereafter significantly inhibited the elevation in IL-1β serum levels (both by 63%, p < 0.005). IL-6 elevation was inhibited by 73% (p < 0.005) when 2-Cl-MGV-1 was administered 30 min before LPS, by 60% (p < 0.05) when co-administered with LPS, and by 64% (p < 0.05) when administered 1 h after LPS. All cytokine assessments were conducted 6 h post LPS injection. Histological analyses showed decreased leukocyte adherence in the lung tissue of the ligand-treated mice. 2-Cl-MGV-1 administration 30 min prior to exposure to LPS inhibited inflammation-induced open field immobility. The beneficial effect of 2-Cl-MGV-1 suggests its potential as a therapeutic option for inflammatory diseases.

TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models.

Introduction Escherichia coli (E. coli) is a significant commensal gram-negative bacterium that can give rise to various diseases. The roles of Toll-like receptor 2 (TLR2) and the NLR pyrin domain-containing 3 (NLRP3) inflammasome in sepsis induced by E. coli infection remain unclear. Methods In vivo, we investigated differences in mortality, production of inflammatory mediators, organ damage, neutrophil count, and bacterial load during E. coli infection in C57BL/6J mice, as well as in mice deficient in TLR2 or NLRP3. In vitro, we investigated the impact of E. coli on the activation of TLR2 and NLRP3 in macrophages and the influence of TLR2 and NLRP3 on the activation of inflammatory signaling pathways and the secretion of inflammatory mediators in macrophages induced by E. coli infection. Results TLR2-deficient (TLR2-/-) and NLRP3-deficient (NLRP3-/-) mice exhibit significantly increased mortality and organ damage after E. coli infection. These mice also show elevated levels of TNF-α and IL-10 in serum and peritoneal lavage fluid (PLF). Additionally, TLR2-/- and NLRP3-/- mice display heightened neutrophil recruitment, increased bacterial load in the blood. Furthermore, macrophages from these mice demonstrate a significant reduction in the activation of the MAPK signaling pathway. Conclusion TLR2 and NLRP3 play crucial roles in modulating inflammatory mediator expression, immune cell recruitment, and bactericidal activity, thereby preventing excessive tissue damage and reducing mortality in E. coli-induced sepsis.

An Observational Study on Clinical Benefits of CytoSorb in Patients with Severe Sepsis

Background and Aim: Sepsis is a well-recognized healthcare issue worldwide. Despite research, the ability to positively influence outcome remains limited. Newer evidences have pointed that using adsorption of cytokines is beneficial during endotoxemia and sepsis. Therefore, this study was aimed to determine the clinical benefits of CytoSorb usage in patients with severe sepsis admitted in intensive care units (ICU). Study Design: Prospective, observational, comparative study. Material and Methods: Forty patients with sepsis admitted to ICU were included. The CytoSorb group included 20 patients who received CytoSorb therapy in addition to Standard-care (SOC) and 20 patients in SOC group who received SOC alone as per routine ICU protocols. Clinical and laboratory parameters were analyzed pre/post-treatment in both groups and compared. Results: CytoSorb and SOC groups were comparable at baseline. There was significant reduction in serum creatinine (2.59±2.0 vs. 2.89±1.2, mg/dl; P=0.042), serum lactate (3.26±1.1 vs. 3.27±0.9, mmol/lit; P&lt;0.001), serum procalcitonin (2.75±2.4 vs. 3.39±3.5, ng/ml; P&lt;0.001), serum CRP (90.2±57.4 vs. 175.6±100.9, mg/dl; P&lt;0.001) and serum IL6 (1769.7±4444.1 vs. 256.8±392.4, pg/ml; P=0.03) levels in CytoSorb compared to SOC. There was significant improvement in mean arterial pressure (MAP) (65.75±1.8 vs. 62.75±2.8, mmHg; P&lt;0.001) and reduction in norepinephrine dose (6.47±2.7 vs.10.65±3.6, mcg/min; P&lt;0.001) in CytoSorb group reflecting better hemodynamic stability. The post-treatment increase in SOFA score was lesser in CytoSorb group (11.85±2.9) than SOC group (12.3±2.3), but was not significant (P=0.135). Conclusion: CytoSorb therapy along with SOC was associated with significant improvements in hemodynamic stability, MAP and Norepinephrine requirements than SOC alone in severe sepsis.

TVNS alters inflammatory response in adult VPA-induced mouse model of autism: evidence for sexual dimorphism.

Autism is a neurodevelopmental disorder with limited treatment alternatives and which incidence is increasing. Some research suggests that vagus nerve simulation might lead to the reduction of certain symptom. Therefore, we aimed to examine the effect of bilateral transcutaneous auricular vagus nerve stimulation (tVNS) on the inflammatory response in an adult valproic acid (VPA) induced mouse (C57BL6) model of autism for the first time. The autism model was induced by oral VPA administration (600 mg·kg-1) to C57BL/6 pregnant mice on E12.5 days. The study included three groups: the VPA Transcutaneous Auricular Stimulation Group (VPA + tVNS), the VPA Control Group (VPA + sham), and the Healthy Control Group (Control + sham). Each group included 16 mice (8 M/8 F). Our results show that serum IL-1β and IL-6 levels were significantly higher in male VPA-exposed mice than controls. However, IL-1β was significantly lower, and IL-6, TNF- α, and IL-22 were not different in female VPA-exposed mice compared to the control group. Brain NLRP3 levels were significantly higher in both sexes in the VPA autism model (P < 0.05). tVNS application increased brain NLRP3 levels in both sexes and reduced serum IL-1β levels in male mice. We conclude that cytokine dysregulation is associated with the VPA-induced adult autism model, and the inflammatory response is more pronounced in male mice. tVNS application altered the inflammatory response and increased brain NLPR3 levels in both sexes. Further studies are needed to understand the beneficial or detrimental role of the inflammatory response in autism and its sexual dimorphism.

Treatment of post-stroke fatigue with point-toward-point insertion of elongated needle and Tongdu Tiaoshen therapy of acupuncture: a randomized controlled trial

To observe the effect of point-toward-point insertion of elongated needle on post-stroke fatigue and explore its underlying mechanism. Sixty-four patients with post-stroke fatigue were randomly divided into an observation group (32 cases, 2 cases dropped out) and a control group (32 cases, 2 cases dropped out). In addition to the conventional treatment of western medicine and rehabilitation exercises, Tongdu Tiaoshen (regulating the governor vessel and the spirit) therapy of acupuncture was used in the control group, and acupuncture was applied to Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Fengfu (GV 16) and bilateral Fengchi (GB 20) and the needles were retained for 30 min in one treatment. In the observation group, besides the interventions as the control group, point-toward-point insertion of elongated needle was adopted. The needle was inserted from Zhiyang (GV 9) toward Dazhui (GV 14), from Shendao (GV 11) toward Yaoyangguan (GV 3) and from Yaoqi (EX-B 9) toward Yaoyangguan (GV 3); and the needles were retained for 30 min in one treatment. In the two groups, the acupuncture was delivered once daily, 6 times a week, consecutively for 4 weeks. The scores of the fatigue severity scale (FSS), Pittsburgh sleep quality index (PSQI), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Fugl-Meyer assessment (FMA) were observed before and after treatment completion in the two groups. Using ELISA, the levels of serum interleukin (IL)-1β, IL-6, IL-10, high-sensitivity C-reactive protein (hs-CRP), and homocysteine (Hcy) were detected before and after treatment completion; and clinical effect was evaluated. The scores of FSS, PSQI, HAMA and HAMD, as well as the levels of serum IL-1β, IL-6, hs-CRP and Hcy were reduced (P<0.05), and the scores of FMA and the levels of serum IL-10 were increased (P<0.05) after treatment in comparison with those before treatment in the two groups. Compared with the control group, in the observation group, the scores of FSS, PSQI, HAMA and HAMD, and the levels of serum IL-1β, IL-6, hs-CRP and Hcy were reduced (P<0.05, P<0.01), and the score of FMA and the level of serum IL-10 were increased (P<0.05). The total clinical effective rate was 83.3% (25/30) in the observation group, which was higher than 73.3% (22/30) of the control group (P<0.05). The point-toward-point insertion of elongated needle alleviates fatigue, anxiety and depression, and ameliorates sleep and motor function in the patients with post-stroke fatigue. It may be related to the attenuation of inflammatory responses.

CGF therapy: bridging androgenetic alopecia observations to psoriasis treatment via IL-17 pathway.

Concentrated Growth Factor (CGF), rich in CD34 + stem cells, is widely used in treatments for androgenetic alopecia and skin rejuvenation due to its immune-modulating properties. Psoriasis, a chronic inflammatory skin condition, presents significant treatment challenges, particularly for patients who cannot use biologics due to conditions such as cancer and lesions resistant to treatments. The potential of CGF in treating psoriasis is promising, given its broad immunoregulatory effects which confirmed in our previous androgenetic alopecia work. We evaluated the impact of CGF on IL-17 levels in two contexts: patients treated for androgenetic alopecia and a psoriasis mouse model. Twelve patients received three monthly injections of CGF, with serum IL-17 levels measured before and after treatment. In the psoriasis mouse model, groups were treated with CGF, and outcomes were assessed using the Psoriasis Area and Severity Index (PASI), skin barrier scores, histological analysis, and RNA sequencing. Additionally, in vitro experiments applied CD34 + cells from CGF to keratinocytes to measure levels of TNF-α, IFN-γ, IL-23, and IL-17. In patients with androgenetic alopecia, three monthly CGF injections resulted in significantly reduced serum IL-17 levels. In the psoriatic mouse model, CGF-treated groups exhibited lower PASI scores and improved skin barrier scores compared to controls. Histological analysis revealed enhanced skin characteristics, while RNA sequencing demonstrated downregulated IL-17 and upregulated CD34 expression, as well as improved expression of barrier-related genes. In vitro, the application of CD34 + cells from CGF to keratinocytes led to a significant reduction in TNF-α, IFN-γ, IL-23, and IL-17 levels, indicating strong anti-inflammatory effects. A clinical case of a psoriasis patient unresponsive to IL-23 therapy (Guselkumab) showed significant improvement following CGF treatment. These findings indicate that CGF could serve as an effective and versatile treatment for psoriasis, especially for patients who have already undergone biologic therapies but continue to experience resistant lesions.

Palygorskite improves growth performance and prevents liver damage in avian pathogenic Escherichia coli-challenged broiler chickens at an early age.

Avian pathogenic Escherichia coli (APEC) is a major bacterial infection that causes economic losses in the global poultry industry. Palygorskite (PAL) has been shown to enhance growth performance while improving antioxidative and anti-inflammatory properties of broilers. This study evaluated the protective effects of PAL on growth performance and liver function in broilers subjected to APEC challenge. A total of 320 one-day-old male Arbor Acres chicks were divided into four groups with eight replicates of ten birds each, based on a 2×2 factorial arrangement (basal diet or 5g/kg PAL-supplemented diet) and inoculation (bacterial culture medium or APEC). PAL increased body weight gain (BWG) prior to APEC challenge (P < 0.05). However, APEC caused losses in BWG, feed intake (FI), and feed efficiency, along with increased relative hepatic weight, hepatic pathology scores, and hepatic-cell apoptosis rate (P < 0.05). Compared to normal birds, APEC increased interleukin (IL)-1β, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and nitric oxide (NO) levels, as well as lysozyme (LZM) and myeloperoxidase (MPO) activities, while decreasing total antioxidant capacity (T-AOC) and IL-10 levels, and total superoxide dismutase (T-SOD) and catalase (CAT) activities in both serum and liver, APEC also raised alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, but reduced total protein (TP), albumin (ALB), immunoglobulin (Ig) A, IgG, and IgM levels in serum (P < 0.05). Moreover, APEC increased hepatic mRNA level of IL-1β, IFN-γ, TNF-α, nuclear factor kappa B, and inducible nitric oxide synthase (iNOS), while inhibited mRNA level of IL-10 (P < 0.05). In contrast, PAL increased BWG and FI, alleviated hepatic-cell apoptosis rate during the challenge period (P < 0.05). An incorporation of PAL reduced triglyceride and NO contents, ALT and AST activities, while increasing TP, ALB, IL-10, IgG, and IgM levels in serum, enhancing serum T-SOD and CAT activities, elevating hepatic T-AOC and CAT activities, inhibiting hepatic MDA accumulation, and reducing IL-1β levels and LZM activity in both liver and serum (P < 0.05). An interactive effect was found for hepatic TNF-α and iNOS mRNA expression, in which PAL inhibited their mRNA expression in APEC-challenged birds (P < 0.05). Overall, PAL addition partially mitigated the negative impact of APEC challenge on growth performance and liver function of broiler chicks at an early age.

Yoga Intervention and Inflammatory Homoeostasis in Breast Cancer Patients

Objectives: Yoga, renowned for its ability to maintain physical, mental and spiritual well-being, has recently gained prominence as a supportive therapy during conventional breast cancer (BC) treatment. This paradigm shift reflects a growing trend of people embracing yoga to enhance their overall health and aid in managing BC. The objective of this study was to determine the yoga intervention and inflammatory homoeostasis in newly diagnosed BC patients. Materials and Method: This study recruited 44 newly diagnosed BC patients at stages II, III and IV (without distant metastasis or other inflammatory diseases), all admitted for neoadjuvant chemotherapy followed by surgery. A prospective non-randomised control design was employed. Baseline assessments were conducted before the first chemotherapy cycle, with follow-ups before the 2nd and 3rd chemotherapy cycles, before surgery, and 2 months post-surgery. The outcome was compared with the control group. Results: The study showed significant within-subject effects in the yoga intervention group on serum tumour necrosis factor-alpha, interleukin (IL)-1-beta and IL-6 levels, while no significant changes were observed in the control group. Although between groups did not show statistically significant, the mean values indicated a consistent downregulation of proinflammatory markers over time in the yoga group. Conclusion: Incorporating yoga as a complementary therapy alongside conventional BC treatment significantly improved the health outcomes of BC patients by modulating proinflammatory markers.

5114 Establishment of Thyroid Storm Mouse Model and Therapeutic Effects of Ghrelin

Abstract Disclosure: C. Kurimoto: None. Y. Furukawa: None. T. Akamizu: None. A. Doi: None. K. Takeshima: None. S. Morita: None. H. Iwakura: None. H. Ariyasu: None. H. Furuta: None. M. Nishi: None. T. Matsuoka: None. Context: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, is caused by a combination of thyrotoxicosis and severe physical stresses. Infection is the most common triggering factor. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. Further, TS has limited therapeutic options. Objectives: We aimed to confirm the hypercytokinemia in patients with TS, establish a TS model mouse by triiodothyronine and lipopolysaccharide administration, and explore the therapeutic effects of ghrelin on TS. Methods: We evaluated serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. As a TS model, C57BL/6 mice were titrated with triiodothyronine and lipopolysaccharide to develop a lethal model with approximately 30% survival at 24 hours. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin on these parameters. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease without TS (55.7 ± 69.0 vs. 3.13 ± 1.41 pg/mL, P &amp;lt; .05, n=4 each). Next, we titrated the doses of T3 and LPS, aiming to achieve a survival rate of approximately 30% at 24 hours after administration. Two out of five mice in the T3 3.0 mg/kg group died, while none of the eight mice in the T3 1.0 mg/kg group died. Therefore, we determined that the appropriate T3 dose for the TS mouse model is 1.0 mg/kg, which is not lethal when administered alone. In the T3 1.0 mg/kg group (n=8), serum FT3 levels were approximately three times higher (15.3 ± 4.5 vs. 4.5 ± 0.7pg/ml) than those in the control group (n=8). Next, different doses of LPS was added to the T3 group. Survival at 24 hours post-dose was 60% in the T3 + LPS 0.2 mg/kg group (n=5) and 33% in the T3 + LPS 0.5 mg/kg group (n=5), while survival was 100% in the LPS 0.5 mg/kg alone group (n=5),. Based on these findings, the dosage for the murine TS model was determined to be “triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg”. This TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin at 300 µg/kg improved the survival rate to 66.7% (P &amp;lt; .01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We confirmed the hypercytokinemia in patients with TS. Next, we established a lethal model simulating TS by inducing “thyrotoxicosis” by exogenous administration of thyroid hormones, and by inducing “sepsis” by intraperitoneal administration of LPS. The model mice exhibited similar pathophysiological status to human TS associated with induction of serum IL-6 and other biomarkers, which were improved by ghrelin. Presentation: 6/1/2024

BML-111 Modulates and Alleviates p38/MAPK Signaling Pathway and Th1/Th2/Th17 Cytokine Response in Murine Psoriasis-Like Dermatitis.

Psoriasis is a prevalent cutaneous inflammatory disorder characterized by elevated keratinocyte inflammation. 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), an established analogue of lipoxin A4, is known for its potent anti-inflammatory properties. However, the precise role of BML-111 within a murine psoriasis-like dermatitis model requires further clarification. This research aims to investigate the modulatory effects of BML-111 on inflammatory responses, the p38/mitogen-activated protein kinase (MAPK) signaling cascade, and T helper type 1 (Th1), Th2, and Th17 cell responses within the context of a murine psoriasis-like dermatitis model. A psoriasis-like dermatitis model was established by applying 5% imiquimod (IMQ) cream to the backs of C57BL/6 mice, which were pretreated intraperitoneally with or without BML-111 prior to IMQ application. Hematoxylin-eosin staining was utilized to detect the pathological alterations of the murine dorsal skin tissue. Furthermore, the psoriasis area and severity index (PASI) scoring system was used to assess the dynamic cutaneous alterations in the mice. The levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6, IL-4, and IL-17A in the murine serum samples were quantified by means of enzyme-linked immunosorbent assays (ELISA). Western blotting was conducted to detect the proteins of TNF-α, IL-1β, IL-6, phospho-p38 (p-p38), and p38 in murine skin tissues. Lastly, a flow cytometry analysis was executed to evaluate the expression of peripheral blood Th1/Th2/Th17 cell subsets. BML-111 attenuated IMQ-induced pathological changes in skin tissue of psoriasis-like dermatitis mice. BML-111 treatment substantially reduced TNF-α, IL-1β, IL-6, IFN-γ and IL-17A levels and elevated IL-4 levels in serum and skin lesion tissues of IMQ-induced mice (p < 0.01, p < 0.01, p < 0.01, p < 0.05, p < 0.05, p < 0.05, respectively). The ratio of Th1/Th17 cells in the peripheral blood of BML-111-treated mice was substantially diminished and the ratio of Th2 cells was substantially augmented (p < 0.05, p < 0.01, p < 0.001, respectively). Mechanistically, p-p38 protein level was substantially reduced in the skin tissues of BML-111-treated mice (p < 0.05). While, dehydrocorydaline (DHC, a p38/MAPK pathway agonists) reversed the reduction of p-p38 protein level induced by BML-111 treatment in psoriasis-like mice (p < 0.05). BML-111 modulates the p38/MAPK signaling pathway and Th1/Th2/Th17 cytokine response, and alleviates psoriasis-like dermatitis in mice.

Potential of Pre-Operative Serum Interleukin-6 as a Biomarker for Colorectal Cancers

The diagnosis of colorectal cancers (CRC) at its early stage is challenging due to lack of early markers. Current diagnostic tests are either invasive or show low sensitivity. Interleukins are known to elevate and play important roles in the development and progression of the CRC. The studies on interleukin profiles of CRC patients are mainly confined to Caucasian populations while South Asian data are sparse. Therefore, the aim of this study was to investigate the serum IL-6 and IL-10 levels in a cohort of Sri Lankan CRC patients and explore their potential to be used as markers for early diagnosis/prognosis of CRC. Blood samples from 35 CRC patients and 35 healthy volunteers were obtained after informed consent. Their clinical findings and carcinoembryonic antigen (CEA) levels were recorded. Concentrations of IL-6 and IL-10 were measured using ELISA according to manufacturer’s protocols. Mean serum [IL-6] was found to be significantly higher in CRC patients than controls (p&lt;0.05). The mean [IL-10]showed no difference to that of controls. (p&gt;0.05). Interestingly, the [IL-6] in CRC patients were correlated with the disease stage (Stage I-0.16pg/ml; stage II-7.01pg/ml; stage III-15.8pg/ml and stage IV-35.48pg/ml). CEA levels were not correlated with the disease stage or withIL-6 levels. This study provided preliminary evidence to use IL-6 as a potential biochemical marker for the diagnosis of CRC inaddition to CEA. Furthermore, IL-6 could be a marker for prognosis of CRC. Further studies with higher patient samples are needed to validate the results of this study.

Xiaoyin-anshen formula alleviates psoriasis complicated by sleep disturbances by regulating melatonin, antioxidant enzymes, and pro-inflammatory cytokines in mice.

Psoriasis is a common autoimmune and chronic inflammatory dermatological disease that is mainly associated with aberrant immune response and oxidative stress (OS). OS, a crucial pathogenic factor in psoriasis, contributes to psoriasis-like inflammation mediated by the IL-23/IL-17 inflammatory axis. Sleep disturbances (SDs), highly prevalent in patients with psoriasis, exacerbate the condition by disrupting circadian rhythms and reducing melatonin levels, thus promoting OS and inflammation. Xiaoyin-Anshen formula (XYAS), a traditional Chinese medicine (TCM) formula, is composed of the Liangxue-Jiedu (LXJD) and Qingxin-Anshen (QXAS) TCM compounds and has been demonstrated to be effective in treating psoriasis complicated by SDs. However, its exact pharmacological mechanism remains uncertain. Thus, this study used animal experiments to verify whether XYAS can exert therapeutic effects on the disease by regulating melatonin (MLT) levels, protecting against OS, and inhibiting psoriasis-like skin inflammation. A mouse model for psoriasis combined with SDs was established by smearing 62.5mg of 5% imiquimod (IMQ) cream for seven consecutive days, along with a daily injection of p-chlorophenyl alanine (PCPA) solution at a dosage of 300mg/kg at days 6-7. The IMQ cream was continued to be used for maintaining the model at days 8-14. Mice were randomly divided into groups: control, model, MLT, XYAS, LXJD, QXAS. Each group was treated according to its designation at days 8-14, receiving either an oral gavage of XYAS/LXJD/QXAS solution at a dosage of 2mL/100g per day, or a daily injection of MLT solution at a concentration of 0.25mg/mL, with a dosage of 5mg/kg. Immunohistological analysis, pentobarbital-induced sleep test, Western blotting, and enzyme-linked immunosorbent assay (ELISA) were performed to assess and compare pathological features, sleep conditions, localization and/or levels of manganese-dependent superoxide dismutase (mnSOD), mitochondrial cytochrome c (Cyt-C), MLT, retinoid-related orphan nuclear receptor-α (RORα), and pro-inflammatory cytokines interleukin (IL)-6, IL-17A, and tumor necrosis factor-alpha (TNF-α) among groups. MLT, XYAS, LXJD, and QXAS exhibited varying therapeutic effects on RORα regulation, OS inhibition, mitochondrial protection, and anti-inflammation. Compared to the model, the lesion severity/thickness and serum IL-6, IL-17A, and TNF-α levels were gradually reduced in the MLT, QXAS, LXJD, and XYAS. However, no statistical difference in TNF-α levels was identified between the MLT and the model groups. Additionally, skin MLT levels gradually increased in the MLT, QXAS, and XYAS groups, while RORα levels gradually increased in the MLT, QXAS, LXJD, and XYAS groups. All treatments increased mnSOD levels and reduced Cyt-C levels in skin lesions, with XYAS showing the most significant changes. XYAS may treat psoriasis complicated by SDs through two main mechanisms: (1) Improving melatonin-RORα axis in the skin can lead to an increase in mnSOD and a reduction in Cyt-C levels, which provide protection against oxidative stress, mitochondrial damage, and psoriatic inflammation. (2) Reducing IL-6, IL-17A, and TNF-α production to suppress IL-23/Th17 pro-inflammatory signaling axis and epidermal hyperplasia in psoriasis.

The value of serum IL-6 levels in patients undergoing percutaneous coronary intervention and its relation to severity of coronary artery disease by coronary angiography

The value of serum IL-6 levels in patients undergoing percutaneous coronary intervention and its relation to severity of coronary artery disease by coronary angiography

The potential role of interleukin-6 in the association between inflammation and cognitive performance in obstructive sleep apnea

BackgroundInterleukin-6 (IL-6) represents one of the main molecules involved in inflammatory responses, which can be altered in either patients with cognitive impairment or obstructive sleep apnea (OSA). The present study aimed to evaluate serum IL-6 levels and cognitive performance in patients with severe OSA (Apnea-Hypopnea Index - AHI >30/h). MethodsThirty patients with severe OSA were compared to 15 controls similar in age, sex, and Body Mass Index. All patients underwent a sleep medicine interview, including the Epworth Sleepiness Scale (ESS), a polygraphic cardiorespiratory recording, the Montreal Cognitive Assessment (MoCA), and a blood sample for serum IL-6 assessment. ResultsOSA patients presented higher IL-6 serum levels (Md = 7.38) than controls (Md = 2.20, p < 0.001). Moreover, OSA patients showed lower MoCA (Md = 27.00) and higher ESS scores (Md = 8.00) than controls (Md = 30.00, p < 0.001; Md = 4.00, p = 0.004, respectively). Higher IL-6 serum levels were associated with lower oxygen saturation parameters and MoCA scores. ConclusionsThis study documented an association between inflammation, featured by higher IL-6 serum levels, and both nocturnal hypoxemia and cognitive impairment in OSA patients. Therefore, the increase in IL-6 levels may represent the result of vascular damage and neuroinflammation due to intermittent nocturnal hypoxia and further causing neurocognitive dysfunction in OSA.

Diagnoses Bacterial Wound Infection and Detection of Some Immune Parameters in its

This study aims to diagnoses bacterial wound infection and to estimate the serum levels of TLR-3, CXCL8, TGF-β1, IL-8, IL-17 and IL-22 in wound patients. This study had been included 140 samples (blood and swab) obtained from patients found in Baquba-Teaching Hospital from 15/ 6 /2023 to 20 /3 /2024. Swab samples taken from wound were culture on the blood agar and MacConkey agar, and then Bacteria diagnoses was done by using an automatic VITEK 2 system. The serum levels of immune parameters done by ELISA. The results shown that sixty isolates were grow in culture, the results indicated of 38(63.3%) isolates of gram-negative bacteria, represented by: 12 (20%) isolates E. coli, 18 (30%) Pseudomonas aeruginosa, 6 (10%) Protus spp., 2 (3.3%) Acinetobacter spp. the results indicated of 22 (36.6%) isolates of gram-positive bacteria, represented by: 16 (26.6%) isolates Staphylococcus aureus, 4 (6.6 %) another Staphylococcus spp., 2 (3.3%) Enterococcus spp. The study also shown the a increase in the concentration of TLR-3 , CXCL8 , IL-2 , IL-17 and IL-22 in the serum of bacterial patients compared with the healthy, Where the results of the current study show decreases in the concentration of TGF-β1 among compared with healthy. In conclusion, it was discovered that the infection of bacteria in wound infection was lower in females than males. Pseudomonas aeruginosa and S. aureus were found to be the highly isolated bacteria wound infection, with increases levels of TLR-3, CXCL8, IL-17 and IL-22 in serum in patients and decreases level of TGF-β1 in serum of patients.

IL-8, TNF-α, and IL-17 in the Development of Erosive Esophagitis and Symptom Perception in Gastroesophageal Reflux Disease (GERD)

Background: The diverse clinical characteristics of erosive esophagitis (EE) and symptom perception in patients with gastroesophageal reflux disease (GERD) remain a major challenge in understanding their underlying pathogenesis. This study aimed to investigate the association between the levels of IL-8, TNF-α, and IL-17 in serum and the presence of erosive esophagitis and symptoms related to GERD. Method: We enrolled 65 subjects presenting with GERD symptoms. Based on the findings of upper endoscopy, the subjects were categorized into two groups: (1) erosive esophagitis (EE LA grades B-D) and (2) non-erosive esophagitis (normal-EE LA grade A). Symptom perception was assessed via GERD questionnaire (GERD-Q) and the frequency scale for the symptoms of GERD (FSSG). The enzyme-linked immunosorbent assay (ELISA) method was used to analyze serum levels of IL-8, TNF-α, and IL-17. Analysis of cytokine levels between different symptoms severity was performed using the Kruskal-Wallis H test. Results: Median serum IL-8 levels were significantly higher in the erosive esophagitis group compared to those with non-erosive esophagitis (20.2 (IQR 16.9–32.2) vs. 17.7 (IQR 15.2–19.6), p &lt; 0.05). The study found a significant association between IL-8 levels and the presence of globus symptoms (median IL8 level 46.961 (38.622–92.644) in subjects with globus vs. 18.06 (16.68–20.49) in those without globus; p &lt; 0.05). Similarly, TNF-α levels were associated with the frequency of regurgitation symptoms (H index = 10.748; dr = 3; p &lt; 0.05). We observed a significant correlation between IL-17 levels and the frequency of heartburn and early satiety symptoms. Conclusions: IL-8 may play a role in the development of mucosal erosion in GERD. IL-8, TNF- α, and IL-17 might be involved in the development of globus symptoms, the frequency of regurgitation, and the frequency of heartburn and early satiety, respectively. The diverse symptom phenotypes observed in patients with GERD symptoms may be mediated by distinct profiles of proinflammatory cytokines.

Integrating network pharmacology and experimental verification to study the mechanism of Polygonum hydropiper total flavonoids against stress-induced gastric mucosal damage

ContextPolygonum hydropiper L. (P. hydropiper) has outstanding clinical efficacy in treating both acute and chronic gastroenteritis. However, the definite mechanism remains unclear. ObjectiveThis study aimed to explore the potential mechanisms of the total flavonoid of P. hydropiper (FPH) in stress-induced gastric mucosal damage (SGMD) rats through a combination of network pharmacology, molecular docking, and animal experiments. MethodsNetwork pharmacology and molecular docking were utilized to predict the potential mechanisms of FPH against SGMD. In experimental studies, SGMD rat models were established using water-immersion restraint stress (WIRS). FPH was administered at doses of 140, 70, and 35 mg/kg, with ranitidine serving as a positive control, through gavage once daily for 6 consecutive days after model establishment. Stomach and serum specimens were analyzed using HE staining, Western blotting, qPCR, and ELISA to investigate the protective mechanism of FPH in SGMD. ResultsThe network pharmacology analysis identified 16 active ingredients and 183 common targets, with potential pathways including PI3K/Akt, MAPK and Keap1/Nrf2. In vivo experiments demonstrated that FPH intervention alleviated SGMD pathological changes, reduced elevated serum IL-6 and TNF-α levels, and enhanced SOD and GSH activity in rats. Additionally, FPH increased the protein expression of p62, Nrf2, HO-1, PI3K, and p-Akt, along with mRNA levels of Nrf2, p62, and HO-1. ConclusionsFPH exerts a gastric mucosal protective effect by upregulating antioxidant gene expression through the PI3K/Akt and Keap1/Nrf2 pathways. This study provides an experimental basis for the potential clinical treatment of SGMD with the traditional Chinese medicine P. hydropiper.

Diagnostic value of serum vascular endothelial growth factor and interleukin-17 in primary hepatocellular carcinoma.

Despite significant advancements in the medical treatment of primary hepatocellular carcinoma (PHC) in recent years, enhancing therapeutic effects and improving prognosis remain substantial challenges worldwide. To investigate the expression levels of serum vascular endothelial growth factor (VEGF) and interleukin (IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients' clinical characteristics. The study included 50 patients with confirmed PHC who visited Wuhan Hanyang Hospital from January 2021 to January 2022, and 50 healthy individuals from the same period served as the control group. Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay, and their diagnostic value was assessed using receiver operating characteristic (ROC) curves. Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels. Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics. Serum VEGF and IL-17 levels were significantly higher in the study group compared to the control group (P < 0.05). No significant association was observed between serum VEGF and IL-17 levels and gender, age, combined cirrhosis, tumor diameter, or degree of differentiation (P > 0.05). However, there was a significant relationship between clinical TNM stage, tumor metastasis, and serum VEGF and IL-17 levels (P < 0.05). Correlation analysis revealed a positive correlation between serum VEGF and IL-17 (P < 0.05). ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC. Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals. Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage, and there was a significant positive correlation between VEGF and IL-17. These biomarkers may serve as valuable reference indicators for the early diagnosis and treatment guidance of PHC.