Breadth and polyfunctionality of T cell responses to human cytomegalovirus in men who have sex with men: relationship with HIV infection and frailty.

Cytomegalovirus (CMV)-seropositive adults have large T cell responses to a wide range of CMV proteins; these responses have been associated with chronic inflammation and frailty in people with or without HIV infection. We analyzed the relationships between chronic HIV infection, frailty, and the breadth and polyfunctionality of CD4 and CD8 T cell responses to CMV. Peripheral blood mononuclear cells from 42 men (20 without HIV and 22 with virologically suppressed HIV) in the Multicenter AIDS Cohort Study (MACS) were stimulated with peptide pools spanning 19 CMV open reading frames (ORFs). As measured by flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α, and IL-2, CD8 T cells from men with HIV responded to significantly more CMV ORFs than those from men without HIV. This was primarily due to a broader response to ORFs that are expressed during the late phase of CMV replication. The number of ORFs to which a participant's T cells responded was positively correlated with the sum of all that individual's T cell responses; these correlations were weaker in men with than without HIV. Polyfunctional CMV-specific CD4 responses (production of more than one cytokine) were significantly lower in men with than without HIV. Frailty status did not substantially affect the breadth or magnitude of the CMV-specific T cell responses. These results suggest that immune control of CMV infection is affected more by chronic HIV infection than by frailty. The differences between men with and without HIV were similar to those reported between young and older adults without HIV. IMPORTANCE: T cell responses to chronic cytomegalovirus (CMV) infection have significant biological and clinical implications in HIV infection and aging. Here, we systematically analyzed the breadth, magnitude, and polyfunctionality of T cell responses to multiple CMV antigens in men with and without HIV in the Multicenter AIDS Cohort Study (MACS), a longstanding study of the natural and treated history of HIV-1 infection in men who have sex with men. We found that the breadth and polyfunctionality of T cell responses to CMV were different between men with chronic, treated HIV and those without HIV. The reason for these differences is unknown, but these findings suggest that people with treated HIV may have more frequent CMV reactivation than people without HIV. Differences between people with and without HIV also resembled differences reported between young and older adults without HIV, supporting a role for the immune responses to CMV in the aging process.

Interleukin-mediated therapies in liver diseases and comorbidity effects.

Cytokines like interleukins (ILs) play important roles in inflammation and innate immune. Yang and Zhang carried out an interesting study related to ILs and hepatic diseases. They described the role of ILs in the pathogenesis and resolution of hepatic disorders. The authors summarized alcohol-related liver disease and virus-induced hepatitis, as far as clinical studies a fortiori carried out on IL-mediated treatments pertaining to these dysfunctions. This editorial contributes to the review by Yang and Zhang titled, "Interleukins in liver disease treatment", and focuses on therapies mediated by ILs in comorbid liver diseases. The documentary search was conducted on recent pertinent literature, primarily using the Google Scholar and PubMed databases.

Biochemical implication of acetylcholine, histamine, IL-18, and interferon-alpha as diagnostic biomarkers in hepatitis C virus, coronavirus disease 2019, and dual hepatitis C virus-coronavirus disease 2019 patients.

Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID-19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL-18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL-18 function can help understand COVID-19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. angiotensin-converting enzyme 2 (ACE-2) receptors on cholangiocytes suggest liver involvement in SARS-CoV-2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL-18, and interferon-Alpha as diagnostic tools in HCV, COVID-19, and dual HCV-COVID-19 pathogenesis. The current study was a prospective cross-section conducted on 188 participants classified into the following four groups: Group 1 COVID-19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV-COVID-19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL-18, and interferon-alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV-COVID-19 had high ferritin levels compared to other biomarkers while those with COVID-19 infection had high levels of D-Dimer. The histamine, acetylcholine, and IL-18 biomarkers in both COVID-19 and dual HCV-COVID-19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN-Alpha test performed well in the HCV-COVID-19 group and was fair in the COVID-19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL-18, and interferon-Alpha in HCV, COVID-19, and dual HCV-COVID-19 infection. Circulating levels of acetylcholine, histamine, IL-18, and interferon-Alpha can be potential early indicators for HCV, COVID-19, and dual HCV-COVID-19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases.

Immunology of Cytokine Storm Syndromes: Natural Killer Cells.

Natural killer (NK) cells are innate immune lymphocytes that rapidly produce cytokines upon activation and kill target cells. NK cells have been of particular interest in primary hemophagocytic lymphohistiocytosis (pHLH) since all of the genetic defects associated with this disorder cause diminished cytotoxic capacity of NK cells and T lymphocytes, and assays of NK cell killing are used clinically for the diagnosis of HLH. Herein, we review human NK cell biology and the significance of alterations in NK cell function in the diagnosis and pathogenesis of HLH.

Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in promoting osteoclastogenesis, tumor proliferation, and angiogenesis. These cytokines create a favorable environment for cancer cell survival and bone degradation, contributing to the progression of metastatic lesions. Conversely, anti-inflammatory interleukins, including IL-4, IL-10, and IL-13, exhibit protective roles by modulating immune responses and inhibiting osteoclast activity. Understanding these opposing effects is crucial for developing targeted therapies aimed at disrupting the pathological processes in bone metastases. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, mediate the actions of these interleukins, influencing tumor cell survival, immune cell recruitment, and bone remodeling. Targeting these pathways presents promising therapeutic avenues. Current treatment strategies, such as the use of denosumab, tocilizumab, and emerging agents like bimekizumab and ANV419, highlight the potential of interleukin-targeted therapies in mitigating bone metastases. However, challenges such as therapeutic resistance, side effects, and long-term efficacy remain significant hurdles. This review also addresses the potential of interleukins as diagnostic and prognostic biomarkers, offering insights into patient stratification and personalized treatment approaches. Interleukins have multifaceted roles that depend on the context, including the environment, cell types, and cellular interactions. Despite substantial progress, gaps in research persist, particularly regarding the precise mechanisms by which interleukins influence the bone metastatic niche and their broader clinical implications. While not exhaustive, this overview underscores the critical roles of interleukins in bone metastases and highlights the need for continued research to fully elucidate their complex interactions and therapeutic potential. Addressing these gaps will be essential for advancing our understanding and treatment of bone metastases in cancer patients.

Causality between various cytokines and asthma: a bidirectional two-sample Mendelian randomization analysis.

Background: Many studies have shown that cytokines play an important role in the pathogenesis of asthma, but their biological effects on asthma remain unclear. The Mendelian randomization (MR) method was used to evaluate the causal relationship between various cytokines [such as interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), colony-stimulating factors (CSFs), transforming growth factor (TGF), etc.,] and asthma. Methods: In this study, inverse variance weighting was used to evaluate the causal relationship between asthma and cytokines. In addition, the reliability of the results is ensured by multiple methods such as MR-Egger, weighted median, MR-Raps, MR-Presso, and RadialMR, as well as sensitivity analysis. Results: The results showed that none of the 11 cytokines was associated with the risk of asthma. In contrast, asthma can increase levels of IL-5 [odds ratio (OR) = 1.112, 95% confidence interval (CI): 1.009-1.224, P = 0.032] and IL-9 (OR = 1.111, 95% CI: 1.013-1.219, P = 0.025). Conclusion: Genetically predicted asthma was positively associated with elevated levels of IL-5 and IL-9, indicating the downstream effects of IL-5 and IL-9 on asthma. Medical treatments can thus be designed to target IL-5 and IL-9 to prevent asthma exacerbations.

Association of Inflammation and Immune Cell Infiltration with Estrogen Receptor Alpha in an Estrogen and Ionizing Radiation-Induced Breast Cancer Model.

Breast cancer is the most diagnosed cancer in the world, and it is the primary cause of cancer death for women. The risk of breast cancer is increased by endogenous factors like hormones and exogenous factors like radiation exposure that causes damage to the mammary epithelial cells leading to an inflammatory response. Chronic inflammation creates a microenvironment composed of, among other factors, chemokines, and interleukins, which promote cancer. The gene expression of the interleukin 1 receptor type 1, the interleukin 1 receptor antagonist, the Interleukin 1 Receptor Accessory Protein, the interleukin 6 cytokine family signal transducer, the C-X-C motif chemokine ligand 3, the C-X-C motif chemokine ligand 5, and the C-X-C motif chemokine ligand 6 were analyzed in an estrogen and radiation experimental breast cancer model. Furthermore, the expression of these genes was correlated with immune cell infiltration, estrogen receptor expression, and their clinical relevance in breast cancer patients based on data provided by The Cancer Genome Atlas database online. Results given by the experimental breast cancer model showed that all genes related to inflammation respond to ionizing radiation alone or in combination with estrogen. On the other hand, the immune response depended on the breast cancer type and on the expression of the gene that encoded the estrogen receptor. Finally, the importance of the expression of these genes in breast cancer is such that high IL1R1 or IL1RAP is strongly related to patient survival. These findings may help to improve the understanding of the role of immune molecules in carcinogenesis and enhance therapeutic approaches.

Long-Term Oral Administration of Hyperimmune Egg-Based IgY-Rich Formulations Induces Mucosal Immune Response and Systemic Increases of Cytokines Involved in Th2- and Th17-Type Immune Responses in C57BL/6 Mice.

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response.

Beta vulgaris Betalains Mitigate Parasitemia and Brain Oxidative Stress Induced by Plasmodium berghei in Mice.

Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host's body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain oxidative stress induced by Plasmodium berghei in male mice. Two protocols were applied in this study: the therapeutic and prophylactic protocols. The results of the therapeutic protocol revealed a significant decrease in the level of parasitemia caused by P. berghei. Additionally, the histopathological changes in various brain regions were markedly improved after treatment with betalains. Regarding the prophylactic protocol, betalains were able to protect the brain tissues from oxidative stress, inflammation, and disrupted neurotransmitters expected to occur as a result of infection by P. berghei. This was demonstrated by modulating the activities of brain antioxidants (SOD and GSH), inflammatory cytokines (IL-6, IL-10, IL-12, TNF-α, and INF-γ), and neurotransmitters (serotonin, epinephrine, and norepinephrine). This study has proven that using betalains as a treatment or as a preventive has a vital and effective role in confronting the brain histopathological, oxidative stress, and inflammatory changes induced by P. berghei infection.

Subcutaneous adipose tissue: Implications in dermatological diseases and beyond.

Subcutaneous adipose tissue (SAT) is the deepest component of the three-layered cutaneous integument. While mesenteric adipose tissue-based immune processes have gained recognition in the context of the metabolic syndrome, SAT has been traditionally considered primarily for energy storage, with less attention to its immune functions. SAT harbors a reservoir of immune and stromal cells that significantly impact metabolic and immunologic processes not only in the skin, but even on a systemic level. These processes include wound healing, cutaneous and systemic infections, immunometabolic, and autoimmune diseases, inflammatory skin diseases, as well as neoplastic conditions. A better understanding of SAT immune functions in different processes, could open avenues for novel therapeutic interventions. Targeting SAT may not only address SAT-specific diseases but also offer potential treatments for cutaneous or even systemic conditions. This review aims to provide a comprehensive overview on SAT's structure and functions, highlight recent advancements in understanding its role in both homeostatic and pathological conditions within and beyond the skin, and discuss the main questions for future research in the field.

[Features of inflammatory endotypes and phenotypes in chronic rhinosinusitis]. / Osobennosti endotipov i fenotipov vospaleniya pri khronicheskom rinosinusite.

Recently, significant progress has been made in identifying the cellular and molecular mechanisms responsible for the pathogenesis of chronic rhinosinusitis (CRS). Cohort studies of CRS have led to advances in the clinical understanding of this disease. New therapeutic agents have been approved or are undergoing clinical trials to expand treatment options for this disease. One of the promising areas in medicine is the provision of personalized clinical care. From this perspective, CRS can be divided into three different endotypes depending on the type of underlying inflammatory response. In the United States, CRS with and without nasal polyps is predominantly characterized as the second inflammatory endotype. CRS with nasal polyps (about 17%) and without nasal polyps (up to 20%) belongs to the 1st and 3rd inflammatory endotypes, respectively. And if for the second inflammatory endotype the effectiveness of targeted biological therapy is beyond doubt, then for the first and third inflammatory endotypes the principles of such conservative therapy are under active development. Moreover, large validated studies to confirm associations between CRS phenotypes and endotypes, as well as to find effective biological markers of inflammatory endotypes, remain to be performed.

Phosphodiesterase-5 Expression in Buccal Mucosa of Patients with Erectile Dysfunction One Year after Radical Prostatectomy.

(1) Background: Radical prostatectomy has a high incidence of erectile dysfunction (ED). The aim was to determine if the expression of the nitric oxide synthase-3/soluble guanylate cyclase/phosphodiesterase 5 axis could be detected in buccal mucosa and if it could be differently expressed in patients with and without ED; (2) Methods: Erectile function from 38 subjects subjected to prostatectomy was evaluated using the International Index of Erectile Function-Erectile Function Domain before and one year after surgery. Nitric oxide synthase (NOS3), ß1-subunit of soluble guanylate cyclase (sGC), phosphodiesterase-5 (PDE-5) expressions, and interleukin-6 and interleukin-10 content were measured in the buccal mucosa. PDE5A rs3806808 gene polymorphism was genotyped; (3) Results: One year after prostatectomy, 15 patients had recovered functional erection, and 23 showed ED. NOS3, ß1-sGC, interleukin-6, and interleukin-10 expressions were not different between patients with and without ED after radical prostatectomy. Buccal mucosa levels of PDE-5 were higher in patients with ED compared to those who recovered erectile functionality. There were no differences found in the genotype of PDE5A polymorphism; (4) Conclusions: One year after prostatectomy, patients with ED had higher PDE5 levels in their buccal mucosa than patients who had recovered erectile function. Rs3806808 PDE5A gene polymorphism was not associated with increased PDE5 expression in buccal mucosa.

The Influence of Analgesic Wound Infiltration on Postoperative Pain and Inflammatory Cytokines in Open Colorectal Surgery: A Randomized Comparative Pilot Study.

Background and Objectives: Surgical wound analgesia has been analyzed in many studies, but few have focused on its relationship with inflammatory markers. As such, we aimed to determine the influence of analgesic surgical wound infiltration in open colorectal surgery on the seric levels of pro- and anti-inflammatory markers and the associated efficacy in postoperative pain control. Materials and Methods: Forty patients who underwent open colorectal surgery were prospectively randomized: group 0, epidural analgesia; group 1, intravenous analgesia (control), group 2, preincision and prelaparoraphy infiltration; and, group 3, prelaparoraphy infiltration. Wound infiltration was performed with ropivacaine. We analyzed the levels of IL-6 and IL-10 cytokines before and 6 h after surgery and their correlation with pain scores. Results: The postoperative Il-6 levels were significantly lower in group 0 than in the control (p = 0.041). The postoperative Il-10 levels were significantly higher in group 3 (p = 0.029) than in the control. Six hours after the operation, the pain scores were significantly lower in all groups than in the control (p = 0.005, p = 0.022, and p = 0.017 for groups 0, 2, and 3, respectively). Pain scores were significantly correlated with Il-10 levels in group 2 (p = 0.047); in group 3, IL-10 levels directly correlated with those of Il-6 (p = 0.026). Conclusions: The analgetic effect of preincisional and prelaparoraphy analgetic infiltration was efficient. The analgetic infiltration of the surgical wound prior to closure stimulates both the inflammatory activator and regulator interleukins.

[Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti-interleukins].

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gastrointestinal tract. The introduction of biologics, particularly anti-interleukin (IL) agents, has revolutionized IBD treatment. This review summarizes the role of ILs in IBD pathophysiology and describes the efficacy and positioning of anti-IL therapies. We discuss the functions of key ILs in IBD and their potential as therapeutic targets. The review then discusses anti-IL therapies, focusing primarily on ustekinumab (anti-IL-12/23), risankizumab (anti-IL-23), and mirikizumab (anti-IL-23). Clinical trial data demonstrate their efficacy in inducing and maintaining remission in Crohn's disease and ulcerative colitis. The safety profiles of these agents are generally favorable. However, long-term safety data for newer agents are still limited. The review also briefly discusses emerging therapies such as guselkumab and brazikumab. Network meta-analyses suggest that anti-IL therapies perform well compared to other biological agents. These agents may be considered first- or second-line therapies for many patients, especially those with comorbidities or safety concerns. Anti-IL therapies represent a significant advancement in IBD treatment, offering effective and relatively safe options for patients with moderate to severe disease.

STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases.

Signal transducer and activator of transcription (STAT) 4 and STAT6 play a crucial role in immune cells by transducing signals from specific cytokine receptors, and inducing transcription of genes involved in cell-mediated and humoral immunity. These two different defense mechanisms against pathogens are regulated by two specific CD4+ T helper (Th) cells known as Th1 and Th2 cells. Many studies have shown that several diseases including cancer, inflammatory, autoimmune and allergic diseases are associated with a Th1/Th2 imbalance caused by increased or decreased expression/activity of STAT4 or STAT6 often due to genetic and epigenetic aberrances. An altered expression of STAT4 has been observed in different tumors and autoimmune diseases, while a dysregulation of STAT6 signaling pathway is frequently observed in allergic conditions, such as atopic dermatitis, allergic asthma, food allergy, and tumors such as Hodgkin and non-Hodgkin lymphomas. Recently, dysregulations of STAT4 and STAT6 expression have been observed in SARS-CoV2 and monkeypox infections, which are still public health emergencies in many countries. SARS-CoV-2 can induce an imbalance in Th1 and Th2 responses with a predominant activation of STAT6 in the cytosol and nuclei of pneumocytes that drives Th2 polarization and cytokine storm. In monkeypox infection the virus can promote an immune evasion by inducing a Th2 response that in turn inhibits the Th1 response essential for virus elimination. Furthermore, genetic variations of STAT4 that are associated with an increased risk of developing systemic lupus erythematosus seem to play a role in defense against SARS-CoV-2 infection.

Signal transducer and activator of transcription (STAT) proteins are important and complex regulators of transcription that mediate many aspects of cellular immunity, proliferation, apoptosis and differentiation. STAT proteins are phosphorylated/activated in the cytoplasm by Janus Kinases (JAKs) a family of nonreceptor tyrosine kinases associated to type I and type II cytokine receptors. There are seven STAT family members that have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. STAT4 is activated by IL-12 after binding with its specific receptor and induces the production in Th1 cells of IFN-γ, which allows these cells to be particularly effective in protecting against viruses and intracellular bacteria. STAT6 is activated by IL-4 and IL-13 and is required for the development of Th2 immune response and for the production of Th2 cytokines IL-4, IL-5, and IL-13 that contribute to humoral response with the synthesis of antigen specific antibodies in B cells. Although STAT4 plays an important role in many physiological functions, an altered expression of this transcription factor, often due to genetic and epigenetic aberrances, has been observed in different tumors and autoimmune diseases. Dysregulation of STAT6 signaling pathway, often caused by genetic mutations in the STAT6 gene, has been observed in several allergic conditions and tumors such as Hodgkin and non-Hodgkin lymphomas.

Effect of continuous positive airway pressure therapy on blood levels of IL-6, IL-10, IL-18, IL-1ß, IL-4, and IL-17 in obstructive sleep apnoea adults: A systematic review, meta-analysis and trial sequential analysis.

INTRODUCTION: Obstructive sleep apnoea (OSA) is a long-term disorder characterized by frequent blockages in the upper respiratory tract during sleep, often leading to abrupt awakenings, with or without a decrease in oxygen levels. The systematic review and meta-analysis aimed to assess the effect of continuous positive airway pressure therapy (CPAP) on blood interleukin (IL) levels of IL-6, IL-10, IL-18, IL-1ß, IL-4, and IL-17 in OSA adults. MATERIALS AND METHODS: The published databases from PubMed, Scopus, Web of Science, and Cochrane Library were searched from 2003 to 2024, without any restrictions. The Review Manager software 5.3 was employed to compute effect sizes, which were presented as the standardized mean difference (SMD) along with a 95% confidence interval (CI). RESULTS: In total, 320 records were identified through database searching; ultimately, 42 articles were included in the qualitative synthesis and then the meta-analysis. The CPAP therapy significantly reduces IL-6 levels, as indicated SMD=0.64 [95% CI: 0.35, 0.93] and P<0.0001. CPAP therapy significantly reduced IL-18 and IL-1ß levels in adults with OSA, but there is no significant difference in IL-10, IL-4, or IL-17 levels. Age, blood sample, body mass index, ethnicity, and treatment duration for IL-6 and apnoea-hypopnea index with IL-10 levels were effective factors in the pooled results. Experimentally, there was an interaction between IL-18 and IL-1ß. CONCLUSIONS: CPAP therapy has a positive impact on inflammatory markers in OSA adults; remarkably, it reduces IL-6 and IL-1ß levels. Nevertheless, more evidence (such as the role of ethnicity) and understanding of interactions are needed.

Clostridium ramosum alone caused Fournier's gangrene in an older Chinese patient with abnormal interleukin levels: A rare case report.

Clostridium ramosum is an uncommon Clostridium but is one of the essential anaerobic bacteria that makes up the intestinal microbiota. A highly variable body temperature, the white blood cell count, or an elusory prognosis can reflect Clostridium ramosum infection, especially in patients with Fournier's gangrene. Fournier's gangrene is a rare soft-tissue infection with necrosis that occurs mainly in the perianal and genital regions, males being more susceptible. Here, we report a 70-year-old Chinese man with Fournier's gangrene and high levels interleukins who suffered from Clostridium ramosum infection, identified and verified by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA sequencing. Fournier's gangrene severity index (FGSI) of the patient was measured once the patient was admitted to hospital. His FGSI was 6, indicating no abnormal condition. He had abnormally high interleukin (IL)-6, IL-8, and IL-10 levels, associated with severe inflammatory conditions. Despite the patient's resuscitation and standardized treatment with antimicrobial drugs, the symptoms did not improve. The patient's condition deteriorated, and he died on hospitalization day 5. Abnormally elevated IL-6, IL-8, and IL-10 levels were a novel finding in a case of Clostridium ramosum infection, leading to Fournier's gangrene. In the present case, a perianal abscess was the predisposing condition for Fournier's gangrene. Close attention should be paid to the isolation and identification of pathogenic Clostridium ramosum during the bacteriological examination of patients with perianal abscesses. IL-6, IL-8, and IL-10 may be critical biomarkers that supplement the FGSI for diagnosing Clostridium ramosum infection leading to Fournier's gangrene in immunosuppressed persons.

Interleukin-2 mediated associations between gut microbiota and acute myeloid leukemia: A population-based mediation Mendelian randomization study.

The relationship between the gut microbiota and acute myeloid leukemia (AML) has been established, but the exact role of interleukin (IL) in mediating this relationship has remained unclear. This study aimed to utilize whether interleukins mediate the relationships between gut microbiota and AML, thereby identifying potential novel targets for future AML treatment. Mendelian randomization (MR) is a method for finding the causality of exposure and outcome. Final instrumental variables were selected based on MR assumptions, and used to judge validity of the results. Our study identified risk and protective factors for AML, and interleukin-related gut microbiota. Finally, mediation MR analyses resulted in Interleukin-2 (IL-2) mediated associations between Clostridiaceae 1, Clostridium sensu stricto 1 and AML, with IL-2 respectively explaining 13.96 % and 12.11 % of the total effect of the aforementioned gut microbiota on AML. Our results successfully identified causal effects between specific gut microbiota, AML, and interleukins, while also elucidating the mediating role of IL-2 in these associations using MR analysis. These findings provide valuable insights into potential therapeutic targets for AML treatment.

Effect of scaling on levels of interleukin 1-beta and clinical periodontal parameters among e-cigarette users and non-smokers: A prospective study.

INTRODUCTION: This cohort study aimed to compare the effect of ultrasonic scaling on the expression of IL-1ß in the gingival crevicular fluid (GCF) among ENDS users and non-smokers (NS) with gingivitis. METHODS: Self-reported current electronic nicotine delivery system (ENDS) users and NS with generalized gingivitis were included in this study. All the patients underwent scaling at the baseline visit (T0). Clinical measures, periodontal parameters [probing depth (PD), plaque index (PI), and bleeding on probing (BOP)], and GCF IL-1ß were measured at T0, after 1 week (T1) and after 3 weeks (T2). Wilcoxon signed rank test was used to assess the changes in the periodontal measurements and IL-1ß levels at different time points and Mann-Whitney U Test was used to compare the two groups. RESULTS: A total of 38 individuals (18 NS and 20 ENDS users) participated in the study. The PD was significantly higher in ENDS users than in NS at baseline. However, the PI and BOP were similar in all groups at baseline. At T1, the PI was significantly lower for NS than for ENDS users (p=0.045). At T2, there were no significant differences in any of the parameters assessed between the two groups. For ENDS users, BOP was significantly lower at T1 than at baseline. For NS, the BOP at T1 and T2 and the PI at T1 were significantly lower than at baseline. There was no difference in the GCF IL-1ß levels in NS and ENDS users at baseline, T1, and T2. At T2, there was a significant reduction in IL-1ß (p<0.05) than at baseline in both groups. CONCLUSIONS: Both ENDS users and NS with gingivitis responded similarly to scaling. GCF IL-1ß levels were significantly higher at baseline (p<0.05) compared with their levels at T1 and T2 for both the groups. CLINICAL TRIAL REGISTRATION: The study was registered on the official website of ClinicalTrials.gov. IDENTIFIER: ID NCT05745324.

Stasis and Inflammation in Varicose Vein Development: An Interleukin-Mediated Process from Intima to Media.

INTRODUCTION: This study investigated the combination of venous stasis and inflammation in varicose vein development. METHODS: The study included patients with primary varicose veins operated using high ligation and stripping of greater saphenous vein. All of them showed reflux at sapheno-femoral junction on preoperative Doppler ultrasound. Mesenteric veins from early or advanced gastric cancer specimens were used as control group. Inflammatory mediators expressed in the venous wall were measured via immunohistochemistry and compared between the two groups. RESULTS: Thirty-five (59.3%) men and 24 women with a mean age of 52.8 years (range, 23-77 years) were included and 29 (49.2%) patients had edema or skin changes according to Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification and reporting standards for chronic venous disorders. The expression of interleukin 6 (IL-6) and transforming growth factor ß1 (TGF-ß1) in intima and those of IL-6 in media of greater saphenous veins increased, with statistically significant differences between the two groups (p < 0.001). IL-6 in media and TGF-ß1 levels in intima were independent predictors of varicose veins (adjusted odds ratios 74.62 and 66.69, respectively). CONCLUSION: Elevated venous pressure represented by reflux on Doppler ultrasound and increased expression of inflammatory cytokines including IL-6 in media and TGF-ß1 in intima are associated with the development of varicose veins.