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Therapeutic antibodies (Abs) have been anticipated as promising alternatives to conventional treatments such as topical minoxidil and oral finasteride for androgenetic alopecia (AGA). Due to the high molecular weight of typical Abs, the half-life of subcutaneous Abs exceeds 2 weeks, allowing an administration intervals of once a month or longer. Direct injection into the areas of hair loss is also feasible, potentially enhancing treatment efficacy while minimizing systemic side effects. However, therapeutic Abs are rarely developed for AGA therapy due to the requirement to be responsiveness to androgens and to exist in the extracellular fluid or cell surface surrounding the hair follicle. In this review, we introduce recent progress of antibody therapeutics in AGA targeting the prolactin receptor, Interleukin-6 receptor, C-X-C motif chemokine ligand 12, and dickkopf 1. As therapeutic Abs for AGA are still in the early stages, targets need further validation and optimization for clinical application.
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Objective: This study aimed to evaluate the predictive value of IL-6 for stroke recurrence in acute ischemic stroke.Methods: Patients who were admitted within 48 h of onset were included. At 3-month, stroke recurrence was assessed. IL-6 levels were measured in serum samples taken upon admission.Results: Out of the 305 patients, 47 (15.4%) experienced a stroke recurrence. The risk of stroke recurrence increased by 8% (OR: 1.08; 95% CI: 1.04-1.11; p < 0.001) for every 1 pg/ml increase in IL-6 serum level, both in unadjusted and adjusted analyses (6%; OR: 1.06; 95% CI: 1.02-1.10; p = 0.001).Conclusion: The study supports the usefulness of IL-6 as a predictive biomarker for stroke recurrence after acute ischemic stroke.
[Box: see text].
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BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly, characterized by severe cognitive impairment and memory loss. Emerging evidence suggests that neuroinflammation plays a significant role in AD pathogenesis, with cytokines like interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) contributing to the disease progression. METHODS: We utilized GEO datasets to identify IL-6 and CXCL8 as pivotal inflammatory markers in AD. In vitro experiments were conducted using SK-N-BE(2)-M17 and THP-1 cell lines treated with IL-6 and CXCL8 to model AD. Additionally, in vivo tests on Amyloid Precursor Protein/Presenilin 1 (APP/PS1) AD mouse models were performed to assess the impact of these cytokines on cognitive functions and brain pathology. RESULTS: The results indicated a significant decrease in cell viability, increased apoptosis, and elevated inflammatory factor secretion following IL-6 and CXCL8 treatment in vitro. In vivo, AD mouse models treated with these cytokines exhibited exacerbated emotional distress, decreased social interaction, impaired cognitive functions, and increased amyloid protein deposition in neural tissues. CONCLUSIONS: The study highlights the detrimental effects of IL-6 and CXCL8 on neuronal health and cognitive functions in AD. These findings suggest that targeting these cytokines could offer potential therapeutic interventions for improving patient outcomes in Alzheimer's disease.
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OBJECTIVE: We investigated the mechanism whereby interleukin-6 (IL-6), an important inflammatory marker, influences trophoblast function during preeclampsia. METHODS: Quantitative PCR and enzyme-linked immunosorbent assay were used to determine the IL-6 mRNA and protein levels, respectively. CCK8 and transwell assays were used to detect how IL-6 affects the proliferation and invasion abilities of HTR-8/SVneo cells respectively; the tube-forming assay was conducted to explore how IL-6 affects the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) after their co-culture with HTR-8/SVneo cells. Using tandem mass tag-based proteomics analysis, we screened for different proteins before and after IL-6 stimulation; Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to investigate the functions and signal pathways associated with these proteins. RESULTS: The IL-6 levels were higher in the placenta of preeclampsia group than in the normal group. IL-6 suppressed the proliferation and invasion of HTR-8/SVneo cells, but promoted the angiogenesis of HUVECs. Seventy differentially expressed IL-6 downstream proteins were identified; these were enriched with various biological processes, molecular functions, cellular components, and biological pathways.Conclusions: IL-6 regulates trophoblast function by interacting with multiple proteins and pathways. Proteomics-based screening serves as a macroscopic approach to clarify the molecular mechanisms associated with preeclampsia.
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Interleucina-6 , Preeclampsia , Proteómica , Trofoblastos , Humanos , Preeclampsia/metabolismo , Femenino , Embarazo , Interleucina-6/metabolismo , Trofoblastos/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Estudios de Casos y Controles , Espectrometría de Masas en Tándem , Proliferación Celular , AdultoRESUMEN
BACKGROUND: We measured postoperative changes in cerebrospinal fluid (CSF) interleukin (IL)-6 levels in subarachnoid hemorrhage (SAH) due to aneurysm rupture and examined factors associated with outcomes and cerebral vasospasm. We used physiologic saline or artificial CSF as the intraoperative irrigation fluid and examined the differences. METHODS: The participants were 16 men and 41 women who were transported to our facility for SAH and underwent surgical treatment during the period from February 2012 through March 2015. In terms of severity, 31 cases were World Federation of Neurological Surgeons (WFNS) grade I-III and 26 cases were grade IV-V. All cases underwent clipping. Physiologic saline and artificial CSF were used as intraoperative irrigation fluid. We placed a ventricular drainage tube intraoperatively and collected CSF daily from postoperative day (POD) 1 through 10 or until drain removal. RESULTS: IL-6 level varied from 74 pg/mL to 407,936 pg/mL and peaked on PODs 1 and 5. Patients with favorable outcomes had significantly lower postoperative IL-6 levels. POD 1 IL-6 level significantly differed in relation to the presence of cerebral vasospasm but was not associated with its timing or severity. Use of artificial CSF was associated with a significantly lower incidence of cerebral vasospasm. Age and WFNS grade were significantly associated with outcome, and use of artificial CSF had a tendency toward favorable outcomes. CONCLUSIONS: Artificial CSF is a potentially useful intervention when managing subarachnoid hemorrhage.
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Interleucina-6 , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Humanos , Hemorragia Subaracnoidea/cirugía , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Masculino , Femenino , Persona de Mediana Edad , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/líquido cefalorraquídeo , Anciano , Resultado del Tratamiento , Biomarcadores/líquido cefalorraquídeo , Índice de Severidad de la Enfermedad , Adulto , Factores de Tiempo , Aneurisma Roto/cirugía , Aneurisma Roto/líquido cefalorraquídeo , Periodo PosoperatorioRESUMEN
Despite unprecedented survival in patients with glioblastoma (GB), the aggressive primary brain cancer remains largely incurable and its mechanisms of treatment resistance have gained particular attention. The cytokine interleukin 6 (IL-6) and its receptor weave through the hallmarks of malignant gliomas and may represent a key vulnerability to GB. Known for activating the STAT3 pathway in autocrine fashion, IL-6 is amplified in GB and has been recognized as a negative biomarker for GB prognosis, rendering it a putative target of novel GB therapies. While it has been recognized as a biologically active component of GB for three decades only with concurrent advances in understanding of complementary immunotherapy has the concept of targeting IL-6 for a human clinical trial gained scientific footing.
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Neoplasias Encefálicas , Glioblastoma , Interleucina-6 , Glioblastoma/terapia , Humanos , Interleucina-6/metabolismo , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Resistencia a Antineoplásicos , Receptores de Interleucina-6 , Factor de Transcripción STAT3/metabolismo , Inmunoterapia/métodosRESUMEN
The main pathogenic features of immunoglobulin A vasculitis (IgAV) are overactive B cells and elevated production of IgA, which requires help from T follicular helper 17 (Tfh17) cells. To evaluate the pathological role of Tfh17 cells in IgAV, we investigated the mechanism responsible for Tfh17 differentiation and explored how to ameliorate IgAV by modulating Tfh17 generation. Peripheral blood mononuclear cells from IgAV patients were analyzed by flow cytometry. In vitro culture was performed to assess the modulation of cytokine-induced phenotypes. IgAV rats were used to explore the therapeutic effects of IL-6 blockade and the regulatory functions of IL-6 in Tfh17 cells. Serum cytokine and IgA levels were measured by ELISA while histopathological changes were evaluated by H&E,PAS or immunofluorescence staining. Frequency of CD4+CXCR5+CCR6+ Tfh17 cells were increased in IgAV patients and associated with disease severity. There was also a significant infiltration of Tfh17 cells in the kidney of human IgAV nephritis patients. IL-6 promoted the dendritic cell production of TGF-ß and Tfh17 differentiation. In IgAV rats, the in vivo blockade of IL-6 signaling inhibited Tfh17 differentiation, resulting in reduction of the germinal center and IgA production. Suppression of Tfh17 cells using IL-6 blockade greatly ameliorated clinical symptoms such as hemorrhagic rash and bloody stool and decreased IgA deposition and mesangial proliferation in the kidney in IgAV rats. Our findings suggest that suppression of Tfh17 differentiation can alleviate IgA-mediated vasculitis and may permit the development of tailored medicines for treating IgAV.
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To evaluate the therapeutic potential of curcumin tagged cilostazol solid nano dispersion in wistar rat streptozotocin-nicotinamide-induced diabetic nephropathy. Cilostazol (CLT), a Phosphodiesterase (PDE) inhibitor has an inhibitory effect on reactive oxygen species (ROS), and Curcumin (Cur), an antioxidant, and anti-inflammatory, are water-soluble. Solid Nano dispersions were developed using the "Box-Behnken Design" and emulsion solvent evaporation procedure to improve the solubility and bioavailability. Streptozotocin (SPZ) and Nicotinamide (NA) caused diabetes in Wistar rats. DN developed 30-45 days after disease induction. All rat groups underwent histological, biochemical and pharmacokinetic evaluation. The optimized batch of Cilostazol Loaded Novel Curcumin Tagged Solid Nanodispersion (CLT-15 SND) estimated renal, lipid, and cytokine profiles better than the conventional batch. CLT-15 SND, given orally to diabetic rats for 45 days, significantly lowered fasting BGL and IL-6 levels and improved lipid and kidney-profile markers and body weight compared to plain Cilostazol Loaded Solid Nanodispersion (CLT-15 WC SND). CLT-15 SND treatment groups showed decreased blood glucose by 3.38 and 9.71 percent, increased body weight by 2.81 and 5.27 percent, improved Interleukin-6 (IL-6) by 21.36 and 18.36 percent, improved urine albumin levels by 5.67 and 14.19 percent and creatinine levels by 3.125 and 37.5 percent, improved serum urea by 30.48 percent, increased serum albumin by 2.59 and 11.18 percent, and decreased creatinine and 5.03 and 8.12 percent, respectively as compared to CLT-15 WC and MP treatment animal groups. CLT and Cur reduced IL-6, kidney, and lipid markers, demonstrating their renoprotective and pancreas-protective effects. CLT and Cur's inhibition may be the mechanism.
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Background: To investigate the predictive value of specific immunoglobulin E (sIgE), interleukin-6 (IL-6) and regulatory T cells (Treg) on the risk of postoperative recurrence in patients with eosinophilic Chronic rhinosinusitis with nasal polyps (EcRswNP). Methods: A total of 198 patients with EcRswNP collected to our Hospital from January 2019 to December 2021 were selected as the research subjects. All patients underwent functional endoscopic sinus surgery. The patients were selected to recurrence group (RG, n = 48) and nonrecurrence group (NRG, n = 150) on the basis of the recurrence after 1 year of follow-up. The related factors of postoperative recurrence of EcRswNP were analyzed. The ROC was used to analyze the dangerous of sIgE, IL-6 and Treg in predicting postoperative recurrence of EcRswNP patients. Results: The proportion of asthma patients, nasal congestion VAS score, and peripheral blood Eos% content in the RG exceeded that in the NRG, and the Organization Neu % and peripheral blood Neu% levels were less than those in the NRGp (P all < 0.05). The serum sIgE and serum IL6 in the RG were higher than those in the NRG, while the level of peripheral blood Treg was lower than that in the NRG (P < 0.05). Logistic regression analysis showed that high levels of serum sIgE, serum IL-6 and low Treg levels were risk factors for postoperative recurrence (P < 0.05). ROC showed that the AUC of peripheral blood sIgE level, IL-6 and Treg levels alone in predicting the dangerous of postoperative recurrence in patients with EcRswNP were 0.786, 0.707 and 0.636, respectively (all P < 0.05); The AUC of combined prediction of peripheral blood sIgE, IL-6 and Treg levels for postoperative recurrence dangerous in patients with EcRswNP was 0.973, indicating that the efficacy of jointed prediction was exceed than that of single prediction (P < 0.05). Conclusions: The high levels of sIgE, IL6 and low Treg levels in patients with EcRswNP before operation will increase the risk of postoperative recurrence, which is a risk factor affecting postoperative recurrence, and the three indicators have good predictive value for predicting postoperative recurrence in patients with EcRswNP, and the combination of the three indicators has better value in predicting postoperative recurrence.
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Background: percutaneous coronary intervention (PCI) has become the mainstay of treatment for atherosclerotic cardiovascular disease (ASCVD). Inflammatory factors have been shown to be involved in the initiation and progression of ASCVD. After PCI, the persistence of inflammation, especially the inflammation released at the target lesion, may affect the stability of non-target lesion plaques. Interleukin-6 (IL-6) is one of the most common inflammatory factors, however studies about the influence of IL-6 on the progression of non-target lesions (NTLs) of coronary artery are limited. This study investigated whether serum IL-6 levels can affect the progression of NTLs after coronary stent implantation. Methods: We performed a retrospective cohort study including 441 patients undergoing coronary angiography (CAG) and stent implantation, who had at least one NTL, between January 2019 and December 2021. They underwent followup CAG 9 to 12 months after PCI. Quartile grouping was based on serum IL-6 levels following readmission. The relationship between serum IL-6 levels and the progression of NTLs after coronary stent implantation was analyzed by using logistic regression analysis and restricted cubic spline regression. Predictive value of IL-6 on NTL progression was evaluated using the receiver operating characteristic (ROC) curve. Results: When compared to the first quartile (Q1) group, the probability of NTL progression was increased in Q2 (adjusted odds ratio (aOR) 3.06, 95% CI 1.29-7.29), Q3 (aOR 3.55, 95% CI 1.52-8.26), and Q4 group (aOR 7.51, 95% CI 3.30-17.05), with a trend test p < 0.001. With the increase of IL-6 levels, the risk of progression of NTLs gradually increased, and there was a non-linear relationship between IL-6 and progression of NTLs (p < 0.001). The ROC curve showed that the critical value of the serum IL-6 level was 12.652 pg/mL (area under the curve is 0.673, sensitivity is 54.5%, specificity is 70.9%, p < 0.05). Conclusions: A high serum IL-6 level is an independent risk factor for the progression of NTLs after coronary stent implantation, and has certain predictive value for the progression of NTLs.
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BACKGROUND: Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Interleukin 6 (IL-6) is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications. AIM: To investigate the relationship among plasma IL-6 levels, risk of ALI, and disease severity in critically ill patients with sepsis. METHODS: This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022. A total of 83 septic patients were enrolled. Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay. The development of ALI and MODS was monitored during hospitalization. Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. RESULTS: Among the 83 patients with sepsis, 38 (45.8%) developed ALI and 29 (34.9%) developed MODS. Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI (median: 125.6 pg/mL vs 48.3 pg/mL; P < 0.001). Similarly, patients with MODS had higher IL-6 levels than those without MODS (median: 142.9 pg/mL vs 58.7 pg/mL; P < 0.001). Plasma IL-6 levels were strongly and positively correlated with APACHE II (r = 0.72; P < 0.001) and SOFA scores (r = 0.68; P < 0.001). CONCLUSION: Elevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI and MODS. Higher IL-6 levels were correlated with greater disease severity, as reflected by higher APACHE II and SOFA scores. These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI and disease severity in patients with sepsis.
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Interleukin-6 (IL-6) detection and monitoring are of great significance for evaluating the progression of many diseases and their therapeutic efficacy. Lateral flow immunoassay (LFIA) is one of the most promising point-of-care testing (POCT) methods, yet suffers from low sensitivity and poor quantitative ability, which greatly limits its application in IL-6 detection. Hence, in this work, we integrated Aushell nanoparticles (NPs) as new LFIA reporters and achieved the colorimetric and photothermal dual-mode detection of IL-6. Aushell NPs were conveniently prepared using a galvanic exchange process. By controlling the shell thickness, their localized surface plasmon resonance (LSPR) peak was easily tuned to near-infrared (NIR) range, which matched well with the NIR irradiation light. Thus, the Aushell NPs were endowed with good photothermal effect. Aushell NPs were then modified with IL-6 detection antibody to construct Aushell probes. In the LFIA detection, the Aushell probes were combined with IL-6, which were further captured by the capture IL-6 antibody on the test line of the strip, forming a colored band. By observation with naked eyes, the colorimetric qualitative detection of IL-6 was achieved with limit of 5 ng/mL. By measuring the temperature rise of the test line with a portable infrared thermal camera, the photothermal quantitative detection of IL-6 was performed from 1~1000 ng/mL. The photothermal detection limit reached 0.3 ng/mL, which was reduced by nearly 20 times compared with naked-eye detection. Therefore, this Aushell-based LFIA efficiently improved the sensitivity and quantitative ability of commercial colloidal gold LFIA. Furthermore, this method showed good specificity, and kept the advantages of convenience, speed, cost-effectiveness, and portability. Therefore, this Aushell-based LFIA exhibits practical application potential in IL-6 POCT detection.
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Colorimetría , Oro , Interleucina-6 , Interleucina-6/análisis , Oro/química , Inmunoensayo/métodos , Colorimetría/métodos , Humanos , Nanocáscaras/química , Resonancia por Plasmón de Superficie/métodos , Nanopartículas del Metal/química , Límite de Detección , Técnicas Biosensibles/métodosRESUMEN
Age-related hearing loss (AHL) is the most common sensory disorder amongst the older population. Inflammaging is a ≈chronic low-grade inflammation that worsens with age and is an early sign of AHL; however, the underlying mechanisms remain unclear. We used electrophysiological and genetic approaches to establish the importance of interleukin 6 (IL-6)-dependent inflammation in AHL. Elevated IL-6 in the cochlea enhanced Cav1.3 calcium channel function in the inner hair cell (IHC) synapse in mice with AHL. IL-6 upregulated the Cav1.3 channel via the Janus kinase-mitogen activated kinase pathway, causing neurotransmitter excitotoxicity and synapse impairment; IL-6 deficiency or the administration of a Cav1.3 channel blocker attenuated this age-related damage, and rescued hearing loss. Thus, IL-6-dependent inflammaging upregulated the Cav1.3 channel in IHCs, contributing to AHL. Our findings could help the comprehensive understanding of inflammaging's effects on AHL, aiding in early intervention to protect against hearing decline.
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Peroxisome proliferator-activated receptor-γ (PPARγ) plays a protective role against brain injury after stroke in mice. However, the relationship between PPARγ gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in PPARγ, rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, Pinteraction = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.
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The cytokine storm syndrome (CSS) associated with systemic juvenile idiopathic arthritis (sJIA) has widely been referred to as macrophage activation syndrome (MAS). In this chapter, we use the term sJIA-associated CSS (sJIA-CSS) when referring to this syndrome and use the term MAS when referencing publications that specifically report on sJIA-associated MAS.
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Artritis Juvenil , Síndrome de Liberación de Citoquinas , Humanos , Artritis Juvenil/complicaciones , Artritis Juvenil/inmunología , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Citocinas/metabolismo , NiñoRESUMEN
As described throughout this book, different triggers can elicit a variety of different cytokine storm disorders that share overlapping clinical features (Fig. 31.1). Even within a particular cytokine storm disorder, multiple different triggers can elicit the syndrome. Like HLH, multicentric Castleman disease (MCD) serves as a great example of this as it can be caused by a viral infection, neoplastic cell population, or an unknown cause. Furthermore, the idiopathic subtype of MCD (iMCD) provides one of the first examples of a cytokine storm disorder that could be abrogated with targeted neutralization of a single cytokine when inhibition with the anti-interleukin-6 (IL-6) receptor monoclonal antibody tocilizumab was shown to effectively treat iMCD in the 1990s. Of course, this "iMCD treatment," tocilizumab, has been used in a variety of cytokine storm settings over the last 30+ years.
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Anticuerpos Monoclonales Humanizados , Enfermedad de Castleman , Síndrome de Liberación de Citoquinas , Enfermedad de Castleman/tratamiento farmacológico , Enfermedad de Castleman/inmunología , Enfermedad de Castleman/patología , Humanos , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/etiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Citocinas/metabolismo , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-6/antagonistas & inhibidores , Receptores de Interleucina-6/antagonistas & inhibidores , Receptores de Interleucina-6/inmunologíaRESUMEN
Interleukin-6 (IL-6) is a pro-inflammatory cytokine elevated in cytokine storm syndromes, including hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). It is also elevated in cytokine release syndrome (CRS) after immune activating cancer therapies such as chimeric antigen receptor (CAR) T-cells or bispecific T-cell engagers (BITEs) and in some patients after infection with SARS-CoV-2. The interaction of IL-6 with its receptor complex can happen in several forms, making effectively blocking this cytokine's effects clinically challenging. Fortunately, effective clinical agents targeting the IL-6 receptor (tocilizumab) and IL-6 directly (siltuximab) have been developed and are approved for use in humans. IL-6 blockade has now been used to safely and effectively treat several cytokine storm syndromes (CSS). Other methods of investigation in effective IL-6 blockade are underway.
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Anticuerpos Monoclonales Humanizados , COVID-19 , Síndrome de Liberación de Citoquinas , Interleucina-6 , Receptores de Interleucina-6 , Humanos , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Interleucina-6/antagonistas & inhibidores , Interleucina-6/inmunología , Interleucina-6/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/inmunología , Receptores de Interleucina-6/antagonistas & inhibidores , Receptores de Interleucina-6/inmunología , SARS-CoV-2/inmunología , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Síndrome de Activación Macrofágica/inmunología , Síndrome de Activación Macrofágica/tratamiento farmacológicoRESUMEN
A vast body of evidence provides support to a central role of exaggerated production of interferon-γ (IFN-γ) in causing hypercytokinemia and signs and symptoms of hemophagocytic lymphohistiocytosis (HLH). In this chapter, we will describe briefly the roles of IFN-γ in innate and adaptive immunity and in host defense, summarize results from animal models of primary HLH and secondary HLH with particular emphasis on targeted therapeutic approaches, review data on biomarkers associated with activation of the IFN-γ pathway, and discuss initial efficacy and safety results of IFN-γ neutralization in humans.
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Síndrome de Liberación de Citoquinas , Inmunidad Innata , Interferón gamma , Linfohistiocitosis Hemofagocítica , Humanos , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/etiología , Interferón gamma/inmunología , Animales , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Inmunidad Innata/efectos de los fármacos , Inmunidad Adaptativa/efectos de los fármacosRESUMEN
Introduction Oral squamous cell carcinoma (OSCC) is associated with high rates of morbidity and mortality. Despite advances in research and treatment, the survival rate of OSCC patients has not changed considerably in recent years. Interleukin-6 (IL-6) is a proinflammatory cytokine that is involved in the development of various cancers including OSCC. The role of IL-6 is being studied in various cancers; however, its exact mechanism of action in OSCC among the South Indian population has not yet been studied. Thus, the current study aims to evaluate and assess the impact of IL-6 on OSCC among the South Indian population. Materials and methods Twenty tissues from OSCC patients and 20 normal tissues surrounding the same area from normal people were gathered from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospital. The tissues were prepared for expression investigations and hematoxylin and eosin staining. The data was presented as mean ± standard deviation, with statistical significance at p<0.05. Results Our results indicate that, in comparison to normal tissues, OSCC samples had increased IL-6 expression levels (p<0.05). Conclusion We conclude that IL-6 has been identified as a key oncogene in the development of tumors and their spread in several types of cancers, including OSCC. Therefore, IL-6 can be used as a potential diagnostic or prognostic biomarker and the use of IL-6 inhibitors can be formulated as a potential treatment for OSCC.
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Amiodarone is a class III anti-arrhythmic drug found to be effective in treating multiple life-threatening arrhythmias, including paroxysmal atrial fibrillation. Despite its effectiveness, amiodarone has been found to result in thyroid dysfunction. Amiodarone-induced thyrotoxicosis (AIT) is classified as type 1, which often develops in those with autoimmune hyperthyroid conditions, or type 2, which occurs because of destructive thyroiditis in an apparently normal thyroid. Differentiating between both types often poses a clinical and therapeutic dilemma, as AIT 1 is treated with thionamides, whereas AIT 2 requires steroids for treatment. We present a case of a patient with AIT who was treated empirically for both subtypes with methimazole and prednisone without clinical improvement. Methimazole was later stopped due to concern for agranulocytosis, and the patient was then treated with cholestyramine, metoprolol, and prednisone. Given persistent thyrotoxicosis, the decision was made to proceed with surgical intervention. The patient underwent a successful total thyroidectomy without complications. The patient's condition clinically improved post-surgery and was discharged home on post-operative day 2 in stable condition. Prednisone was tapered over two weeks, and he was started on a weight-based dose of levothyroxine. He continues to follow up in our clinic for postoperative hypothyroidism and is clinically and biochemically euthyroid.