UNASSIGNED: Colorectal cancer (CRC) is a third  cause of death worldwide. The immune system plays a significant role in the tumor microenvironment and identifying its components involved in cancer development can aid in finding new biomarkers for prognosis, treatment monitoring, and immune-based therapies. Interleukin 13 (IL-13) is a cytokine produced by immune cells that has been implicated in tumor invasion, proliferation, and metastasis. Previous studies have shown that IL-13 causes the phosphorylation of Tyrosine kinase 2 (TYK2), which may contribute to the development and progression of cancer. This study investigated the levels expression of IL-13 and TYK2 in the tissue and serum of CRC patients and explored their possible association with pathological and clinical factors.
UNASSIGNED: 105 patients with CRC and 105 healthy individuals were involved in the study. Tissue and blood samples were collected. The quantitative Real-Time PCR (qRT-PCR) technique was used to assess the expression levels of the IL-13 and TYK2 CRC tissue samples in comparison with the adjacent control tissue.
UNASSIGNED: The expression levels of IL-13 were lower and TYK2 were found to be higher in CRC tissue compared to normal tissue. Additionally, serum levels of IL-13 were decreased in CRC patients while TYK2 levels were elevated. A significant negative correlation was found between the expression levels of IL-13 in both serum and tissue and the cancer stage.
UNASSIGNED: These results suggest that IL-13 and TYKMay 2 play essential roles in CRC development and progression and may serve as potential biomarkers for early detection and treatment.

UNASSIGNED: The Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation. Previous studies have demonstrated that inhibitors of JAK-STAT pathway blocked the activation of mast cells and basophils.
UNASSIGNED: In this study, we investigated the in vitro effects of ruxolitinib, a JAK1/2 inhibitor, on IgE- and IL-3-mediated release of mediators from human basophils, as well as substance P-induced mediator release from skin mast cells (HSMCs).
UNASSIGNED: Ruxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C4) from human basophils. Ruxolitinib also inhibited anti-IgE- and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs.
UNASSIGNED: These results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders.

Keloids, characterized by excessive scar formation following dermal inflammation, pose a therapeutic challenge due to high recurrence rates. Radiation therapy, contraindicated in children, can minimize recurrence post-surgical removal. Dupilumab, which inhibits the pro-fibrotic interleukin-4/interleukin-13 axis, may effectively manage keloids when intralesional corticosteroid injections are unsuccessful. It may also prevent recurrence post-surgery in pediatric patients. This systematic review assesses the efficacy and safety of dupilumab for the treatment of keloids. Through a systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we identified and analyzed outcomes from three case reports and three case series studies, totaling 15 patients. Results indicate variable responses to treatment, including significant improvements, no clinical change, and worsening of keloid symptoms. Additional research is needed to recommend using dupilumab to treat keloids (Grade D). Treatment response variability may be linked to differences in interleukin-4/interleukin-13 activity between active and inactive keloids. Additionally, the unintended promotion of T helper 17 cell differentiation by dupilumab may worsen keloids.

BACKGROUND: Adipose-derived stem cells (ASCs) are multipotent stem cells capable of differentiating into many cell lineages. They play an important role in wound healing by secreting cytokines. Prior studies have demonstrated the presence of proinflammatory cytokines in burn wounds. However, no studies have been performed evaluating the cytokines released by burn wounds with infections. We hypothesized that there is an alteration in the paracrine factors secreted by ASCs in burn wounds with concomitant infections.
METHODS: Adipose tissue was collected from patients with burn injuries at their index operation. ASCs were extracted and grown under standard tissue culture techniques. The supernatant was extracted. Cytokine analyses were performed with multiplex assays. Infection was determined using a burn sepsis protocol. The cytokine profiles of the two groups were compared using a Mann-Whitney U test.
RESULTS: Sixteen patients were enrolled in the study, 50% with bacterial infection (n = 8). There was no significant difference in the baseline demographics of the two groups (P > 0.05). There were significantly lower concentrations of interleukin 13 and interferon gamma (P < 0.05) in burn patients with concomitant infections.
CONCLUSIONS: ASCs are critical to burn wound healing. This study demonstrated diminished production of interleukin 13, an immunoregulatory cytokine involved in the antiinflammatory pathway by downregulating macrophage activity. This study also demonstrated significantly lower levels of interferon gamma in patient with burns and concomitant infection. This cytokine is crucial for antimicrobial defenses.

Dupilumab has been approved to treat a variety of atopic disorders and was the first US FDA-approved medication for the treatment of eosinophilic esophagitis (EoE), initially approved in May 2022, with expansion in use to patients as young as 1 year of age weighing at least 15 kg in January 2024. It is a fully human monoclonal antibody that inhibits both IL-4 and IL-13 signaling, suppressing TH2-mediated proinflammatory cytokines, chemokines and IgE implicated in EoE pathogenesis. Phase II and III trials in EoE have demonstrated histologic, endoscopic and symptomatic improvement in disease activity with an overall favorable safety profile. This article will review the available clinical trial data and real-world efficacy of dupilumab in EoE.
Dupilumab is a biologic medication used for the treatment of eosinophilic esophagitis. Clinical trials have shown that this medication is effective in treating both inflammation in the esophagus and symptoms associated with eosinophilic esophagitis in a high proportion of patients. Dupilumab was well tolerated by the majority of clinical trial patients, though side effects such as injection site redness and swelling have been reported. More serious side effects are overall rare.

BACKGROUND: Lebrikizumab, a high-affinity IgG4 monoclonal antibody that selectively inhibits interleukin-13 with high binding affinity and slow dissociation rate, prevents the formation of the interleukin-4Rα/interleukin-13Rα1 heterodimer receptor signaling complex. Here we report the impact of lebrikizumab on responses to two non-live vaccines in adult patients with moderate-to-severe atopic dermatitis (AD).
METHODS: ADopt-VA (NCT04626297) was a double-blind, placebo-controlled, parallel-group, 16-week, phase 3 randomized study to assess the impact of lebrikizumab treatment on non-live vaccine immune responses, and efficacy and safety of lebrikizumab compared with placebo. Eligible patients included adults from 18 to 55 years of age with moderate-to-severe chronic AD who were randomly assigned 1:1 to lebrikizumab 250 mg every 2 weeks or placebo and stratified according to disease severity. The primary endpoints were the development of a booster response to tetanus toxoid and a positive antibody response to meningococcal conjugate vaccine (MCV), 4 weeks after administration of the corresponding vaccine.
RESULTS: At week 16, 73.6% of patients in the lebrikizumab group (n = 78/106) achieved Tdap booster response compared with 73.4% of patients in the placebo group (n = 58/79). MCV vaccine response was observed in 86.9% of patients in the lebrikizumab group (n = 86/99) and 75.0% of patients in the placebo group (n = 60/80). At week 16, IGA 0,1 with ≥ 2-point improvement from baseline was achieved by 40.6% (n = 51/125) of patients treated with lebrikizumab and 18.9% (n = 23/122) of patients who received placebo (p < 0.001). There was a higher proportion of patients achieving EASI 75 at week 16 in the lebrikizumab-treated patients (58.0%, n = 72/125) compared with placebo (32.7%, n = 40/122, p < 0.001).
CONCLUSIONS: Treatment with lebrikizumab did not impact response to non-live vaccines Tdap and MCV in this study. Lebrikizumab treatment had a significant degree of efficacy compared to placebo across multiple endpoints.
BACKGROUND: ClinicalTrials.gov identifier NCT04626297.

Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signaling-modulating antibodies is variable and is affected by disease course and patient-specific inflammation patterns. Therefore, understanding the role of inflammation on the viral infectious cycle is critical for effective use of cytokine-modulating agents. We investigated the role of the type 2 cytokine IL-13 on SARS-CoV-2 binding/entry, replication, and host response in primary HAE cells in vitro and in a model of mouse-adapted SARS-CoV-2 infection in vivo. IL-13 protected airway epithelial cells from SARS-CoV-2 infection in vitro by decreasing the abundance of ACE2-expressing ciliated cells rather than by neutralization in the airway surface liquid or by interferon-mediated antiviral effects. In contrast, IL-13 worsened disease severity in mice; the effects were mediated by eicosanoid signaling and were abolished in mice deficient in the phospholipase A2 enzyme PLA2G2D. We conclude that IL-13-induced inflammation differentially affects multiple steps of COVID-19 pathogenesis. IL-13-induced inflammation may be protective against initial SARS-CoV-2 airway epithelial infection; however, it enhances disease progression in vivo. Blockade of IL-13 and/or eicosanoid signaling may be protective against progression to severe respiratory virus-induced lung disease.

Chronic obstructive pulmonary disease (COPD) is caused by the inhalation of noxious particles such as cigarette smoke. The pathophysiological features include airway inflammation, alveolar destruction and poorly reversible airflow obstruction. A sub-group of COPD patients have higher blood eosinophil counts (BECs), associated with an increased response to inhaled corticosteroids and increased biomarkers of pulmonary type 2 (T2) inflammation. Emerging evidence shows that COPD patients with increased pulmonary eosinophil counts have an altered airway microbiome. Higher BECs are also associated with increased lung function decline, implicating T2 inflammation in progressive pathophysiology in COPD. We provide a narrative review of the role of eosinophils and T2 inflammation in the pathophysiology of COPD, encompassing the lung microbiome, pharmacological targeting of T2 pathways in COPD, and the clinical use of BEC as a COPD biomarker.

The gut-skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage (CSD) on mouse intestines. Following the CSD model, 4% sodium dodecyl sulfate was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated-dextran. The role of interleukin-13 (IL-13) in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, or innate lymph cell-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut.

暂无摘要。