Decrease In Interleukin-6 Levels Research Articles

(096) UNDERSTANDING THE RELATIONSHIP BETWEEN CHRONIC PAIN AND DEPRESSION IN LOCALIZED PROVOKED VULVODYNIA

Abstract Introduction Localized provoked vulvodynia (LPV) is a disease characterized by chronic pain in the vulva in response to touching the vulvar vestibular epithelium. As with other chronic pain disorders, vulvodynia is often found accompanied with depression, and depressive symptoms aggravate pain severity and persistence. While there is clear evidence of a connection between chronic vulvar pain and depression, the mechanism of this bidirectional relationship is largely unknown. Accumulating evidence suggests that inflammation plays a central role in depression. Since the pathophysiology of LPV also involves inflammation, we aim to better understand these relationships by pharmacologically inhibiting the enzyme that plays a key role in both inflammation and depression: soluble epoxide hydrolase (sEH). Objective To elucidate the role of sEH in localized provoked vulvodynia, which might be involved in the chronic pain and depression comorbidity prevalent in vulvodynia patients, and discuss the clinical significance of using sEH inhibitors, such as 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), for patients suffering from this condition. Methods Vulvar punch biopsies obtained from painful sites within the vulvar vestibule and non-painful sites within the external vulva of 6 LPV patients and 6 age/race-matched healthy controls were used to generate a library of primary fibroblast strains. Cells were treated with the inflammatory instigator interleukin-1β (IL-1β) and TPPU. Quantitative PCR, Western blotting, and enzyme-linked immunosorbent assays were used to assess the effects of sEH inhibition. Statistical analysis was performed using GraphPad Prism 10.0.2. Comparisons among groups were performed using the one-way analysis of variance (ANOVA) or two-way ANOVA, followed by post-hoc Tukey test. Results Vulvodynia patients produce increased levels of pro-inflammatory cytokines, namely interleukin-6 (IL-6) and prostaglandin E2 (PGE2), when compared with controls. Interestingly, mRNA (P = 0.0091) and protein (P = 0.0198) levels of sEH were significantly lower in the painful vestibule of these patients. When sEH was inhibited with TPPU, we observed a significant decrease in IL-6 levels (P = <0.0001), but not PGE2 (P = 0.6452). These preliminary findings are of fundamental importance as cytokines can directly contribute to the development of depressive symptoms. Conclusions Patients with vulvodynia are more likely to develop depressive symptoms than patients without vulvar pain. Likewise, patients with depression are more likely to develop vulvodynia than patients without depression. Our results suggest that sEH may play a role in this bidirectional mechanism, which could serve as a novel therapeutic target for chronic pain and depression comorbidity. Disclosure No.

Evaluating inflammatory outcomes: A systematic review and meta-analysis of aerobic versus resistance exercise interventions

Chronic inflammation is widely recognized as a crucial contributor to the onset and progression of various diseases. Physical activity serves as a nonmedicinal intervention known to influence inflammatory dynamics. The specific effects of distinct exercise types, namely aerobic and resistance training, on inflammatory indices have not been fully delineated. This systematic review with meta-analysis seeks to clarify the relative impacts of these 2 forms of exercise on markers of inflammation. An exhaustive literature review was performed across several databases, including MEDLINE, EMBASE, and the Cochrane Library, to identify randomized controlled trials that assess the impact of aerobic versus resistance training on inflammatory markers. The primary variables of interest were alterations in inflammatory indicators such as C-reactive protein, interleukin-6, and tumor necrosis factor–alpha. We synthesized the data employing a random-effect meta-analytical approach and evaluated heterogeneity using the I² statistic. The literature search culminated in 36 randomized controlled trial with a collective participant count of 3616. Data analyses revealed that aerobic training is associated with a notable decrease in levels of interleukin-6 [standardized mean difference (SMD): −0.13, 95% CI: −0.31 to −0.05] and C-reactive protein (SMD: −0.28, 95% CI: −0.47 to −0.09), whereas resistance training is linked to a significant reduction in tumor necrosis factor–alpha levels (SMD: −0.61, 95% CI: −0.87 to −0.34). The investigation indicates that both aerobic and resistance training modalities play roles in diminishing inflammatory markers, likely through different biological processes. These insights highlight the critical nature of selecting appropriate exercise modalities to manage inflammatory health issues effectively. It is imperative to conduct further studies to unravel the precise mechanisms at play and to refine exercise recommendations for tailored management of inflammation.

Acceleration of Wound Healing in Diabetic Rats through a Novel 3D Organo-Hydrogel Nanocomposite of Polydopamine/TiO2 Nanoparticles and Cu (PDA-TiO2@Cu).

Diabetic wound represents a serious issue with a substantial impact and an exceptionally complex pathology affecting patients' mental health and quality of life. So, we have developed a novel 3D organo-hydrogel nanocomposite of polydopamine/TiO2 nanoparticles and cu (PDA-TiO2@Cu) and examined its efficacy in diabetic wound healing. Forty-five adult male albino rats were divided into normal control rats (non-diabetic rats with non-treated skin wounds), diabetic control rats (diabetic rats with non-treated skin wounds), and organo-hydrogel-treated rats (diabetic wounds treated with topically applied organo- hydrogel once daily). Macroscopic changes of the wound were observed on days 0, 3, 5, 7, and 10 to measure wound diameters. Skin specimens from the wound tissue were taken on days 3, 7, and 10, respectively, and examined histologically and immunohistochemically. Also, the gene expressions of collagen I, Matrix Metalloproteinase-9 (MMP-9), and Epidermal Growth Factor (EGF), and levels of Interleukin 6 (IL-6) and Superoxide Dismutase (SOD) were assessed. Our observed results indicated that the developed patch significantly accelerated the healing time compared to the normal control and diabetic control groups. Moreover, the patchloaded group revealed complete re-epithelization and a highly significant increase in the mean area % of CD31 immunostaining on day 7. The organo-hydrogel-loaded group displayed a significant decrease in gene expression of MMP-9 and a significant increase in gene expression of EGF and collagen I. Additionally, the organo-hydrogel-loaded group exhibited a significant decrease in levels of IL-6 and a significant increase in levels of SOD, compared to the normal diabetic control groups. The organo-hydrogel can be used for treating and decreasing the healing period of diabetic wounds.

EFFECTIVENESS OF CENTELLA ASIATICA EXTRACT ON IL-6 AS BIOLOGICAL MARKER OF POST OPERATIVE WOUND HEALING IN PERIORBITAL REGION

Abstract
 Introduction & Objectives : Centella asiatica (CA) is considered as major herbal plant that beneficial on wound healing process. Wound healing process will stimulate inflammatory cells to release growth factors and cytokines, e.g., interleukin-6 (IL-6). This aim of this study is to determine the effectiveness of CA on IL-6 levels as a biological marker of postoperative wound healing in the periorbital region.
 Methods : A double-blind, randomized controlled study on the first day of postoperative periorbital patients was conducted at the Mohammad Hoesin Hospital in Palembang from March to June 2022. There were 30 patients who met inclusion criteria. The effectiveness of CA and placebo were analyzed using Wilcoxon test, while comparisons of the effectiveness were analyzed using Mann-Whitney test (SPSS ver. 22.0).
 Results : No difference in age, sex, and IL-6 levels before treatment between the CA and placebo groups (p>.05). There was a decrease in IL-6 levels before and after CA administration (p=.005). There was an increase in IL-6 levels before and after giving placebo (p=.031). There was a difference in IL-6 levels between the CA and placebo groups (p=.004) after the intervention.
 Conclusion : There is a difference in IL-6 levels after administration of systemic centella asiatica on periorbital postoperative wound healing in the first week.

Anti-inflammatory effect of Faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1β, and IL-6 in DENV-3-infected Wistar rats.

Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue infection leads to an elevation in the release of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). These three cytokines have been shown to correlate with the development of thrombocytopenia and plasma leakage, which is related to the severity of the disease. This study aims to investigate the effect of faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1β, and IL-6 levels in Wistar rats infected with dengue, specifically DENV-3. A group of 27 male Wistar rats (Rattus norvegicus) aged 2-3 months and weighting 200-300 g were divided into three distinct groups: healthy, dengue, and treatment (dengue infection and extract) groups. The rats in both the dengue and treatment groups were administered an injection of DENV-3 with a titer of 105 pfu at a dosage of 0.8 cc via the intraperitoneal route. The propagation of DENV-3 was initiated using C6/36 cells, and it underwent four passages. The extract was administered orally via a nasogastric tube at a dosage of 1,500 mg/kg body weight once daily for 7 days. The healthy group underwent blood sampling on the first day, whereas the dengue and therapy groups underwent blood sampling on the fifth and eighth, respectively. Compared with the healthy group, TNF-α levels in the dengue and treatment groups showed significant differences on day 5 post-infection. The post hoc analysis revealed a statistically significant difference between the dengue-treatment and dengue-healthy groups. The IL-1β levels in the dengue and healthy groups significantly differed on days 5 and 8 post-infection compared to the healthy group. The treatment group had less of a decrease in IL-6 levels on days 5 and 8 than the dengue group. However, no statistically significant differences were observed. The stem bark of S. quadrifida shows potential as an anti-inflammatory agent in dengue infections, particularly in its ability to decrease levels of TNF-α and IL-1β.

Early and Timely Use of Hemofiltration Therapy with Poly Methyl Meth Acrylate (PMMA) Filters in Severe COVID-19 Adult Respiratory Distress Syndrome Patients: A Single Centre Study in India

A high Interleukin-6 (IL-6) level in COVID-19 plays a major role in the pathophysiology and is considered a reliable parameter in predicting the adversity of the disease. In COVID-19. Extracorporeal blood purification has been proposed as an adjuvant therapy and it aims at controlling the dysregulation in the immune system. Essentially, it lowers the upregulated levels of several mediators and therefore controls the cytokine storm, instead of actively targeting individual pathways of inflammation. Positive IL-6 balance post-Polymethyl methacrylate (PMMA) filter used for Cytokine storm in COVID-19 patients with dialysis has shown to be an independent predictor of mortality. A retrospective analysis of seventeen patients wherein hemofiltration was used for cytokine storm with dialysis, sepsis, and septic shock. The inflammatory markers post-hemofiltration sessions were supervised to understand hemofiltration's efficacy. The average age of the patients was 70.2 (18.2) years. They were classified as responders or non-responder groups based on the decrease or no change/ increase respectively between the pre-and post-filtration IL-6 levels. A 3.6-fold increase was noticed in non-responders (N=11) for IL-6 levels post hemofiltration. Responders demonstrated a 21.4% (p<0.05) reduction in IL-6 levels post hemofiltration. Of these, 4 who survived demonstrated a decrease in IL-6 levels of 66.2%. Of 10 non-responders, none survived. However, the survival rate was 71.43 percent among the responders. There was a significant statistical difference in the mortality rate between the two groups (p= 0.003).Cytokine storm, an overwhelming immunological response in COVID-19 patients, can be controlled successfully by the early and timely use of hemofiltration therapy with PMMA filters like Hemofeel. However, patients with higher positive IL-6 balance post-hemofiltration may be associated with limited outcomes.

Effects of epicatechin on cardiovascular function in middle-aged diet-induced obese rat models of metabolic syndrome.

The current study aimed to investigate the cardiovascular effects of epicatechin, a flavonoid found in green tea and cocoa, in attenuating complications associated with metabolic syndrome in diet-induced obese rats. Male Wistar-Kyoto (WKY) rats aged 16 weeks were fed either standard rat chow or given a high-fat-high-carbohydrate (HFHC) diet for 20 weeks. Epicatechin treatment (5 mg/kg/d) was administered to a subset of WKY rats commencing at week 8 of the 20 week HFHC feeding period. Body weights, food, water and energy intakes, blood pressure, heart rate and glucose tolerance were measured throughout the treatment period. Oxidative stress and inflammatory markers, lipid levels, cardiac collagen deposition, cardiac electrical function, aortic and mesenteric vessel reactivity were examined after the treatment. Twenty weeks of HFHC feeding in WKY rats resulted in the development of metabolic syndrome indicated by the presence of abdominal obesity, dyslipidaemia, glucose intolerance and increased blood pressure. Epicatechin treatment was found to enhance the oxidative stress status in HFHC groups through an increase in serum nitric oxide levels and a decrease in 8-isoprostane concentrations. Furthermore, WKY-HFHC rats displayed a decrease in IL-6 levels. The lipid profiles in HFHC groups showed improvement, with a decrease in LDL-cholesterol and TAG and an increase in HDL-cholesterol levels observed in WKY-HFHC rats. However, epicatechin was not effective in preventing weight gain, glucose intolerance or hypertension in HFHC fed rats. Overall, the results of this study suggest that epicatechin has the potential to improve the underlying mechanisms associated with metabolic syndrome in obese rats.

The anti-inflammatory effect of ferulic acid is via the modulation of NFκB-TNF-α-IL-6 and STAT1-PIAS1 signaling pathways in 2-methoxyethanol-induced testicular inflammation in rats

BackgroundFerulic acid (FAC) is a component of plant cell walls, where it serves as a building block of lignin and pectin. As such, it is abundantly found in vegetables and other plants. In contrast, 2-methoxyethanol (2METH) is a testicular toxin commonly found in products used by humans. This study is aimed to investigate the effect of FAC on 2METH-induced testicular inflammation in rats. MethodFour groups of 5 animals each were used: Group I served as the control, Group II was exposed to 2METH only (100 mg/kg), Group III was administered 2METH (100 mg/kg) plus FAC (50 mg/kg), and Group IV served as the FAC (50 mg/kg) only group. All administrations were done orally for 30 days. ResultsAt the end of the study, rats administered 2METH only showed a significant increase in the testicular levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and nuclear factor κB (NF-κB), as well as RNA gene expressions of Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1), and suppressor of cytokine signaling 1 (SOCS1) compared to the control group. In contrast, treatment with FAC led to a significant decrease in the testicular levels of IL-6, TNF-α, iNOS, COX-2, NF-κB, and gene expression of STAT1, while significantly increasing the testicular gene expression of protein inhibitor of activated STAT 1 (PIAS1) compared to rats exposed to 2METH only. ConclusionBased on the data gathered from this study, FAC demonstrated an anti-inflammatory effect by inhibiting the testicular activation of NF-κB through the downregulation of pro-inflammatory markers (IL-6, TNF-α, iNOS, and COX-2) and the inhibition of the STAT1-PIAS1 signaling pathway in rats.

VAS Scores, Pain-Free Duration, Range of Motion, and IL-6 Levels are Better in Adductor Canal Block Compared to Genicular Nerve Block in Patients with Chronic Pain of Degenerative Disease of the Knee Joint

Introduction: Chronic knee pain is the leading cause of functional limitations in the older age group and accounts for many visits to health care providers. This degenerative condition is progressive with functional impairment and a severe decrease in quality of life. Pain management with Adductor Canal Block (ACB) and Genicular Nerve Block (GNB) can be an alternative treatment option for chronic knee pain. This study aims to analyze the difference between clinical & laboratory outcomes of the ACB and GNB groups. Material & Methods: An experimental study with consecutive sampling was conducted on 34 patients with chronic knee pain divided into 2 groups of ACB and GNB procedures. The parameters measured were VAS score, pain-free duration, range of motion, and interleukin-6 (IL-6) levels. Results: Predominance of chronic knee pain patients found in older women. Based on statistical analysis, there was an improvement in VAS scores (p<0,05), a similar pain-free duration (p>0,05), an improvement in the range of motion (p<0,05), and a decrease in IL-6 levels (p<0,05) significantly in the ACB group compared to GNB. Conclusion: ACB can be used as an effective therapy in treating chronic knee pain.

Regulatory T cell enhancement in adults with cystic fibrosis receiving Elexacaftor/Tezacaftor/Ivacaftor therapy.

Cystic fibrosis (CF), especially CF lung disease, is characterized by chronic infection, immune dysfunction including impairment of regulatory T cells (Tregs) and an exaggerated inflammatory response. CF transmembrane conductance regulator (CFTR) modulators have shown to improve clinical outcomes in people with CF (PwCF) with a wide range of CFTR mutations. However, it remains unclear whether CFTR modulator therapy also affects CF-associated inflammation. We aimed to examine the effect of elexacaftor/tezacaftor/ivacaftor therapy on lymphocyte subsets and systemic cytokines in PwCF. Peripheral blood mononuclear cells and plasma were collected before and at three and six months after the initiation of elexacaftor/tezacaftor/ivacaftor therapy; lymphocyte subsets and systemic cytokines were determined using flow cytometry. Elexacaftor/tezacaftor/ivacaftor treatment was initiated in 77 PwCF and improved percent predicted FEV1 by 12.5 points (p<0.001) at 3 months. During elexacaftor/tezacaftor/ivacaftor therapy, percentages of Tregs were enhanced (+18.7%, p<0.001), with an increased proportion of Tregs expressing CD39 as a marker of stability (+14.4%, p<0.001). Treg enhancement was more pronounced in PwCF clearing Pseudomonas aeruginosa infection. Only minor, non-significant shifts were observed among Th1-, Th2- and Th17-expressing effector T helper cells. These results were stable at 3- and 6-month follow-up. Cytokine measurements showed a significant decrease in interleukin-6 levels during treatment with elexacaftor/tezacaftor/ivacaftor (-50.2%, p<0.001). Treatment with elexacaftor/tezacaftor/ivacaftor was associated with an increased percentage of Tregs, especially in PwCF clearing Pseudomonas aeruginosa infection. Targeting Treg homeostasis is a therapeutic option for PwCF with persistent Treg impairment.

The Effect of Vitamin C Administration on Interleukin-6 in Male Rats of Wistar Strain Infected with Pseudomomonas Aeruginosa Bacteria

Pseudomonas aeruginosa is the main pathogen that causes nosocomial infections in hospitals, and can infect open wounds, burns to necrosis pneumonia. Research shows vitamin C contains antioxidants and antimicrobials. To determine the effect of vitamin C administration on reducing interleukin-6 (IL-6) in male rats of wistar strains infected with Pseudomonas aeruginosa bacteria. This study used an experimental research design with a Post Test Only Control Group Design research design. The subjects of the study amounted to 30 wistar rats which were randomly divided into 5 groups. K(-) group of rats without P. aeruginosa infection. K(+) group of rats infected with P. aeruginosa 108 CFU per head without vitamin C. P1, P2 and P3 in P. aeruginosa infection and given vitamin C at doses of 9 mg, 18 mg and 36 mg/mL/day for 7 days. Day 8 examination of IL-6 levels using the ELISA method. The results of IL-6 levels the One Way Anova test showed significant differences between groups (p = 0.028). The decrease in IL-6 levels in the K3 group infected with Pseudomonas aeruginosa bacteria and vitamin C at a dose of 9 mg/ml/ day experienced insignificant differences with the control group (K1), the K4 group given vitamin C at a dose of 18 mg/ml/day and the K5 group given vitamin C at a dose of 36 mg/ml/day.

The effects of Rhus coriaria L. (sumac) and Cinnamomum zeylanicum L. bark on serum cytokine levels in rat mammary carcinogenesis.

The purpose of this study was to assess the potential effects of Rhus coriaria L. (sumac) and of Cinnamomum zeylanicum L. bark on the selected serum cytokines as possible serum tumor markers - interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the rat model of mammary carcinogenesis. R. coriaria and C. zeylanicum bark were used as the chemopreventive-therapeutic agents taken by rats in the powder form in the diet at two different concentrations during the entire period of two experiments carried out separately: lower concentration 1 g/kg - 0.1% and higher concentration 10 g/kg - 1%. The serum levels of cytokines of IL-6, IL-10, and TNF-α were determined using an enzyme-linked immunosorbent assay. In the first experiment treated with R. coriaria, a significant decrease in serum levels of IL-6 and TNF-α was present at higher concentrations compared to the chemoprevention-free control group. R. coriaria at lower concentrations non-significantly reduced the serum levels of IL-6 and TNF-α when compared to controls. A significant decrease in serum levels of TNF-α was present at higher concentrations compared to lower concentrations. The significant effect of R. coriaria on the serum levels of IL-10 was not observed. In the second experiment treated with C. zeylanicum bark, a significant decrease in serum levels of IL-6 was observed in lower and higher concentrations compared to the chemoprevention-free control group. C. zeylanicum bark non-significantly reduced the serum levels of TNF-α and had no effect on the serum levels of IL-10. In conclusion, R. coriaria and C. zeylanicum bark demonstrated significant anti-inflammatory effects by analyzing the selected serum cytokine levels in the rat breast carcinoma model. Observed anti-inflammatory effects of both plant-natural substances were associated with their anticancer activities in rats.

Follow-up of Interleukin 6 and Other Blood Markers during the Hospitalization of COVID-19 Patients: A Single-Center Study

COVID-19 is a recent respiratory illness with high morbidity and mortality; therefore, the study and characterization of blood markers associated with the improvement or deterioration of COVID-19 patients are crucial. This study compared levels of interleukin 6 (IL-6), procalcitonin (PCT), D-dimer, cortisol, dehydroepiandrosterone sulfate (DHEA-S), c-reactive protein (CRP), 25-OH vitamin D, anti-SARS-CoV-2 IgG antibodies, and viremia in mild–moderate and severe–critical COVID-19 patients. In addition, the time course of blood markers was studied in severe–critical cases. The results show that levels of IL-6, PCT, D-dimer, and CRP, the cortisol/DHEA-S ratio, as well as positive viremia and anti-Spike IgGs were higher in severe–critical patients requiring hospitalization. During follow-up, most severe–critical cases displayed similar time patterns of IL-6 and viral load, whereas anti-SARS-CoV-2 antibody curves showed an inverse pattern. A decrease in IL-6 levels was associated with the improvement of COVID-19 patients, mostly through a reduced oxygen requirement. This preliminary study suggests that an increase in serum IL-6, PCT, D-dimer and CRP levels and the cortisol/DHEA-S ratio could support the selection of patients with poorer prognosis and the need for an intensive or alternative treatment. Additionally, changes in IL-6 during hospitalization were associated with changes in patient’s status mainly with a decrease in oxygen requirements, which indicates that serial measurements of IL-6 could predict the outcome of severe–critical patients with COVID-19 pneumonia.

The Effect of N-Acetylcysteine as Adjuvant Therapy of Hypoxemia in COVID-19 Patients, Assessed by Interleukin-6 Level and PaO2/FiO2 Ratio

Background: Interleukin 6 (IL-6) is a cytokine that plays an essential role in lung damage and mortality. Arterial-to-inspired oxygen (PaO 2 /FiO 2 ) ratio, also known as the Horowitz index, is a measure of hypoxemia in respiratory failure. N-Acetylcysteine (NAC) might be helpful in managing coronavirus disease 2019 (COVID-19) patients by decreasing the cytokine storm, which will lead to a decrease in disease severity. This study aims to analyze the effect of NAC as adjuvant therapy on IL-6 level and PaO 2 /FiO 2 ratio in COVID-19 patients. Methods: This is a quasi-experimental, non-equivalent control group designed study of confirmed COVID-19 patients moderate to critical in Saiful Anwar Hospital Malang. Seventy-five patients received NAC intravenously 5000mg/72 hours as adjuvant therapy for seven days, and 16 subjects in the control group. IL-6 level and PaO 2 /FiO 2 ratio were measured on day one and day 8 in both groups from blood samples. Wilcoxon, Mann-Whitney U Test, and Pearson correlation were conducted for statistical analysis. Results: The decrease in IL-6 level on days 1 to 8 in the NAC group is significantly lower (94.49±253.51) than in the control group ( P =0.002). The increase in PaO 2 /FiO 2 ratio from day 1 to day 8 in the NAC group is significantly improving (126.94±76.05), the same as the control group ( P &lt;0.001). There is a weak correlation between IL-6 level and PaO 2 /FiO 2 ratio after administration of NAC (r=0.154, P =0.186). Conclusion: There is a significant decrease in IL-6 level after administration of NAC. NAC has no significant effect on hypoxemia in COVID-19 patients.

Changes in plasma levels of IL-6 and D-dimer in high-risk thrombosis cancer patients undergoing chemotherapy

Background: Cancer and chemotherapy are venous thromboembolism (VTE) risk factors. The immune system and inflammation are essential in cancer-associated thrombosis's pathogenesis. Chemotherapy can induce inflammatory conditions that trigger the nuclear factor kappa B (NF-κB) signaling pathway to produce proinflammatory cytokines. Interleukin 6 (IL-6) improves procoagulant status primarily by inducing tissue factor (TF) expression. Tissue factor expression triggers the coagulation system, characterized by increased levels of D-dimer. This study assessed the change in plasma levels of IL-6 and D-dimer changed in high-risk thrombosis cancer patients undergoing chemotherapy. Methods: This study was a prospective cohort study of 54 newly diagnosed high-risk thrombosis cancer patients undergoing chemotherapy in Dr. Kariadi General Hospital from January 2021 to September 2021 based on inclusion and exclusion criteria. IL-6 and D-dimer concentrations were collected a day before and after chemotherapy. IL-6 measured by ELISA method and D-dimer measured by the turbidimetry chromogenic immunoassay method. We did correlation test, compared mean, and subgroup analysis. The p-value&lt;0.05 was significant. Results: There was a positive correlation between plasma levels of IL-6 and D-dimer both pre- and post-chemotherapy (r=0.36; 95% CI (0.1-0.6); p=0.006 and r=0.45; 95% CI (0.2-0.6); p=&lt;0.001, respectively). Post-chemotherapy plasma IL-6 (61.0±84.9 pg/mL) was significantly lower (p=0.022) than pre-chemotherapy (102.4±141.6 pg/mL). Subgroup analysis based on risks of thrombosis showed a significant decrease in plasma levels of IL-6 in the higher risk cancer group of thrombosis post-chemotherapy compared with the low risk cancer group (77.7±144.1 pg/mL vs -0.9±127.8 pg/mL; p=0.037). There was an increase in D-dimer plasma levels post-chemotherapy, but it was not statistically significant (2598.1±2487.8 µg/ml vs 3098.6±3547.4 µg/ml; p=0.512). The subgroup analysis based on blood type, tumor stage, chemotherapy regimen, and risk of thrombosis showed no significant differences in delta plasma IL-6 and D-Dimer levels pre- and post-chemotherapy. Conclusion: In high-risk thrombosis cancer patients who underwent chemotherapy, there was a statistically significant decrease in plasma levels of IL-6 post-chemotherapy. There was an increase in D-dimer plasma levels post-chemotherapy, but it was not statistically significant.

Assessment of the Anti-inflammatory Activities of the Moringa Leaf Extract in Periodontitis Cases through IL-6 Cytokine Analysis in Wistar (Rattus novergicus)

BACKGROUND: Periodontitis is a chronic inflammatory disease that causes damage to the supporting structures of the teeth, and if left untreated, it can lead to impaired function, appearance, pain, and tooth loss. Periodontitis is caused by bacteria that adhere to and grow on the tooth surface. The “red complex” bacteria consisted of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. These bacteria will trigger an inflammatory response in the body. Interleukin-6 (IL-6) is an IL that acts both as a pro-inflammatory cytokine, IL-6 is a stimulator for MMP production. To treat the periodontal disease can be through non-surgical therapy as well as surgical therapy, to maximize therapy, it is accompanied by antimicrobial therapy. However, because of the frequent use of antimicrobials, causing antimicrobial resistance in patients, the use of natural ingredients as additional therapy is very necessary for this study using Moringa leaves as a substitute for antimicrobials. AIM: This study aimed to determine the effectiveness of Moringa leaf in influencing the anti-inflammatory cytokine IL-6. The first benefit of this research is to provide scientific information in the field of dentistry regarding the effectiveness of Moringa leaves against red-complex bacteria P. gingivalis as a cause of chronic periodontitis through anti-inflammatory cytokine analysis. METHODS: The type of research that will be used is quasi-experimental with a post-test research design with a control group design. This study used a sample consisted of 30 Wistars (Rattus novergicus) and was divided into two groups based on periodontal tissue sampling as follows treatment group which was treated with extracts Moringa and control group with aquadest irrigation after bacterial induction in the gingival sulcus. Blood samples were taken on days 0, 1, 3, 5, and 7 and centrifuged obtain blood serum and serum cytokine levels (pg/mL) were quantified using a commercial ELISA IL-6 kit. RESULTS: This study obtained the results that there was a decrease in IL-6 in both groups on the 3rd day of observation (D3) where the treatment group given Moringa extract showed a greater decrease in IL-6 levels compared to the control group. There is a significant value in the comparison of IL-6 levels between the two groups with p-value: 0.000 (p &lt; 0.05). CONCLUSION: Moringa oleifera leaf extract showed the anti-inflammatory effect on inflammation induced by the bacterium P. gingivalis. M. oleifera extract can reduce the production of the pro-inflammatory cytokine IL-6 induced by P. gingivalis bacteria in periodontitis.

Curcumin as adjuvant therapy to improve remission in myeloma patients: A pilot randomized clinical trial.

Background:The treatment for ineligible transplant multiple myeloma is melphalan prednisone. Curcumin has an anti-inflammatory and antiangiogenesis in cancer-directed to nuclear factor-kappa B (NF-kB) pathway. Interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and lactate dehydrogenase (LDH) were also involved in the pathogenesis of myeloma. No clinical study has evaluated the efficacy of curcumin in myeloma patients. To evaluate the efficacy of curcumin as adjuvant into melphalan prednisone in myeloma patientsMethods:33 myeloma patients at Dr. Kariadi General Hospital, Semarang, Indonesia during 2016-2017 were randomly assigned single-blindedly into MPC (n=17) and control group (n=16). The MPC group was treated with melphalan 4 mg/m2, prednisone 40 mg/m2 for 7 days, and curcumin 8 gram daily for 28 days. The MP control group was treated with melphalan, prednisone, and placebo. The primary endpoint was the overall remission. Pre- and post-treatment was examined for NF-κB, VEGF, TNF-α, IL-6, LDH, and CRP levels All data analyses were per protocol.Results:There was a significant difference in overall remission between the MPC and MP control groups [75%vs 33.3%, x2=6.89, P=0.009]. A significant decrease of NF-κB, VEGF, TNF-α levels were shown in the MPC group compared with the MP control group. There was a significant decrease in IL-6 levels in a subgroup analysis of the MPC group. TNF-α levels had a significant correlation with remission [OR=1.35; (95%CI=1.03-1.76); P=0.03].Conclusion:Curcumin has an efficacy in improving overall remission and decreasing NF-κB, VEGF, TNF-α, and IL-6 levels in myeloma patients.

The effect of 4% mangosteen peel extract gel on interleukin-6 (il-6) levels and clinical parameters in stage iii grade b periodontitis patients

Interleukin-6 (IL-6) is a proinflammatory cytokine that is produced locally in inflamed tissues after the activation of lipopolysaccharides and other cytokines such as in patients with periodontitis. Mangosteen peel extract gel application as a form of local application therapy contributed to the reduction of IL-6 and clinical parameters in stage III grade B periodontitis patients. This study aimed to analyze the effect of 4% mangosteen peel extract gel as additional scaling and root planing therapy on IL-6 levels in patients with stage III grade B periodontitis. This study was a pre and posttest control group design study with the number of samples divided into 2 groups. This study used 4% mangosteen peel extract gel which was administered locally into the subgingival after scaling and root planing and placebo gel was used as a comparison. Gingival crevicular fluid was taken before and after treatment in each group and IL-6 levels were measured using the ELISA kit Bioassay. The mean decrease in IL-6 levels before and after subgingival aplication of 4% mangosteen peel extract gel was significant (p

Relationship of Anti-interleukin-6 Receptor Antibody to Interleukin-6 Level and Inducible Nitrite Oxide Levels in Peripheral Nerve Injury in Chronic Constriction Injury-Induced Rats: A Case-Control Study in Indonesia

BACKGROUND: Interleukin-6 (IL-6) and inducible Nitric oxide Synthase (iNOS) have an effect on neuropathic pain in the inflammatory process in peripheral nerve injuries. AIM: This study aims to examine the effect of anti-IL-6 receptor antibody on IL-6 and iNOS levels as a consideration for the treatment of neuropathic pain in a rat model of peripheral nerve injury. METHODS: Twenty-eight young adult male Wistar rats were treated for peripheral nerve injury and then divided into two groups. Fourteen treatment groups (Group P) were given anti-IL-6 receptor antibody by injection at a dose of 100 g/day by injection into the saphenous vein in the rat’s leg for 3 days. In both groups, the serum IL-6 and iNOS levels were assessed on the 3rd day after administration of anti-IL-6 receptor antibody in group P, using the sandwich ELISA method. RESULTS: The results showed that the administration of anti-IL-6 receptor antibody did not have a significant effect on reducing IL-6 and iNOS levels in group P (p &gt; 0.05). Administration of anti-IL-6 receptor antibody had more effect on IL-6 levels on iNOS levels, where a decrease in IL-6 levels caused a decrease in iNOS levels in group P (p = 0.004 and r = 0.693). CONCLUSIONS: We conclude that the present administration of anti-IL-6 receptor antibody cannot be considered as a treatment for neuropathic pain in peripheral nerve injuries, but can be used to influence IL-6 levels on iNOS levels.

A 1-year follow-up study on immunological changes following deep brain stimulation in patients with epilepsy

The aim of this study was to evaluate the effects of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) on systemic inflammatory responses in patients with drug-resistant epilepsy (DRE). Twenty-two Finnish patients with ANT-DBS implantation were enrolled in this pilot study. Changes in plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels were examined using generalized estimating equation models at seven time points (before DBS surgery and 1, 2, 3, 6, 9 and 12 months after implantation). In the whole group, the IL-6/IL-10 ratio decreased significantly over time following ANT-DBS, while the decrease in IL-6 levels and increase in IL-10 levels were not significant. In the responder and nonresponder groups, IL-6 levels remained unchanged during the follow-up. Responders had significantly lower pre-DBS IL-10 levels before the ANT-DBS treatment than nonresponders, but the levels significantly increased over time after the treatment. In addition, responders had a higher pre-DBS IL-6/IL-10 ratio than nonresponders, and the ratio decreased for both groups after treatment, but the decrease did not reach the level of statistical significance. The rate of decrease in the ratio per month tended to be higher in responders than in nonresponders. These results may highlight the anti-inflammatory properties of ANT-DBS treatment associated with its therapeutic effectiveness in patients with DRE. Additional studies are essential to evaluate the potential of the proinflammatory cytokine IL-6, the anti-inflammatory cytokine IL-10, and their ratio as biomarkers to evaluate the therapeutic response to DBS treatment, which could facilitate treatment optimization.