Interleukin Research Articles

The Association of Interleukin-36 Staining Intensity and Response to Biologic Therapy in Patients With Psoriasis: A Retrospective Immunohistochemical and Chart Review Pilot Study.

There are limited surrogate biomarkers to identify the active inflammatory pathway in psoriasis to direct treatment with targeted biologic therapies. We investigated the association of interleukin (IL)-36 epidermal expression, a diagnostic marker of psoriasis, with response to biologic therapy in patients with psoriasis. Retrospective immunohistochemical and chart review pilot study. Patients with psoriasis with low (scores 0-2) vs. high (scores 3-4) IL-36 expression did not have significantly different response rates to tumor necrosis factor α (TNFα), IL-17, and IL-12/23 or IL-23 inhibitors; and similarly, mean IL-36 expression scores did not significantly differ among responders vs. non-responders to each treatment mechanism. However, in patients with psoriasis treated with IL-12/23 or IL-23 inhibitors, there was a marked absolute difference in response rates in those with high vs. low IL-36 (84% vs. 50%, p = 0.12) and in mean IL-36 scores in responders vs. non-responders (3.35 vs. 2.57, p = 0.19). Patients with psoriasis with high IL-36 expression were more likely to respond to IL-12/23 and IL-23 inhibition than those with low IL-36, though these findings were not statistically significant. Additional studies with larger sample sizes are needed to validate and expand upon these findings.

A case of peeling skin syndrome type 1 with novel CDSN gene variation successfully treated with upadacitinib.

Peeling skin syndrome type 1 (PSS1) is an autosomal recessive genodermatosis caused by the CDSN gene loss-of-function mutation and characterized by widespread superficial skin peeling and erythroderma with unbearable pruritus. Because of its ultra-rarity and unclear mechanism, this rare disease has no established treatment regimen. Herein, we reported a Chinese woman who presented with congenital generalized pruritic erythroderma and exfoliation, notable for significantly elevated IgE levels. The whole exome sequencing identified an unpublished homozygous variant (c.295C>T, p.Gln99*) in the CDSN gene, confirming the diagnosis of PSS1. Immunohistochemistry analysis of the affected skin confirmed the lack of corneodesmosin expression, revealed the overexpression of T helper 2 (Th2)-related cytokines harboring interleukin (IL) 4 and IL-13. After Janus kinase 1 (JAK1) inhibitor upadacitinib administration, both the patient's skin rashes and itching symptoms were significantly alleviated. Our work expanded the PSS1-related CDSN gene mutation spectrums, substantiated the hypothesis regarding the overexpression of Th2-related cytokines, and uncovered the important role of JAK1 underlying PSS1. JAK1 signaling may dominate the pathogenesis in PSS1 and represent a potential therapeutic target.

Increased CD14+HLA-DR-/low myeloid-derived suppressor cells can be regarded as a biomarker on disease severity and response to therapy in acute coronary syndrome.

This study aimed to investigate the dynamic changes in monocytic myeloid-derived suppressor cells (M-MDSCs) and their implications in the pathogenesis of acute coronary syndrome (ACS), shedding light on potential therapeutic targets. Peripheral blood samples were collected from 68 ACS patients, 35 stable angina pectoris (SAP) patients, and 30 healthy controls (HC). Multi-parameter flow cytometry was employed for analysis of M-MDSCs, explored with disease characteristics and progression. ACS patients exhibited an increased frequency of circulating M-MDSCs compared to SAP patients and HC. M-MDSCs levels demonstrated associations with ACS type, coronary artery lesions, multi-vessel disease, and cardiac dysfunction severity. Higher M-MDSCs levels were found in obese patients. Notably, therapy led to a significant decrease in M-MDSCs frequency. Furthermore, ACS patients exhibited elevated levels of interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in the cytokine profile associated with M-MDSCs. Increased expression of arginase-1(Arg-1) was observed in ACS patients, with positive correlations between M-MDSCs levels and IL-6, GM-CSF, and Arg-1 expression. The diagnostic performance of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and M-MDSCs levels varied in predicting the severity of coronary artery stenosis, with TG showing higher specificity, HDL-C displaying higher sensitivity, and M-MDSCs levels demonstrating balanced sensitivity and specificity. Assessment of M-MDSCs frequency holds promise as a predictive marker for disease progression and therapy response of coronary artery stenosis. The elevated presence of M-MDSCs suggests their potential role in modulating ACS-related inflammation.

Differences in the DNA methylome of T cells in adults with asthma of varying severity

BackgroundDNA methylation plays a critical role in asthma development, but differences in DNA methylation among adults with varying asthma severity are less well-defined.ObjectiveTo examine how DNA methylomic patterns differ among adults with asthma based on asthma severity and airway inflammation.MethodsPeripheral blood T cells from 35 adults with asthma in Beijing, China, were serially collected over time (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Differential methylation was compared among subjects with varying airway inflammation and severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume in one second (FEV1), and Asthma Control Test (ACT) scores.ResultsSignificant differences in DNA methylation were noted among subjects with different degrees of airway inflammation and asthma severity. These differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function and included gene ontology categories related to MHC class II assembly, T cell activation, interleukin (IL)-1, and IL-12. Genes related to P450 drug metabolism, glutathione metabolism, and developmental pathways were also differentially methylated in comparisons between subjects with high vs low FEV1 and ACT. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, AGT, PTPRC, PTPRJ, and several genes downstream of the JAK2 and TNF signaling pathway.ConclusionThese findings demonstrate how adults with asthma of varying severity possess differences in peripheral blood T cell DNA methylation that contribute to differences in clinical indices of asthma.

MTORC2 inhibition by JR-AB2-011 improves IL-1β-induced inflammation, catabolic response, and apoptosis in human chondrocytes through IκB-α/NF-κB p65.

Osteoarthritis (OA) is a very common chronic joint condition marked by inflammation and cartilage loss. mTOR is a well-known mediator of inflammation, cell survival, and aging; however, its role in OA has not been determined. To explore the role of mTORC2 in OA-and associated pathological changes, we examined the contribution of mTORC2-mediated Akt, rictor and IκB-α/NF-κB p65 pathway in interleukin (IL)-1β-treated human chondrocytes. We focused on the protein expression of proinflammatory cytokines and catabolic and apoptotic factors, including TNF-α, IL-6, iNOS, MMP13, Bax, and caspase3, which may occur through this signalling pathway in IL-1β-treated chondrocytes. Chondrocytes were cultured and treated with either 2 ng/mL IL‑1β alone or in combination with increasing concentrations of JR-AB2-011 (50, 100, or 250 µM), a selective mTORC2 inhibitor. The protein levels of phosphorylated (p)‑Akt, Akt, rictor, p-NF-κB p65, NF-κB p65, IκB-α, p-IκB-α, iNOS, MMP13, Bax, and caspase3 were evaluated by Western blotting. In IL-1β-stimulated chondrocytes, mTORC2 activity was increased with increased phosphorylation of Akt and expression of rictor. IL-1β increased the expression of p-IκBα, p-NF-κB p65, NF-κB p65, IL-6, TNF-α, iNOS, Bax, and caspase3 proteins and decreased the expression of IκB-α. All of these IL-1β-induced alterations were prevented by JR-AB2-011. The main novel finding in the present study is that selective mTORC2 inhibition by JR-AB2-011 prevents the inflammatory, catabolic, and apoptotic responses induced by IL-1β via modulation of IκB-α/NF-κB activity. Therefore, we demonstrated a previously unknown function of mTORC2 inhibition that seems to be a potential therapeutic target for OA.

Effect of N-acetylcysteine in treatment of COPD with pulmonary interstitial fibrosis, inflammatory factors and VEGF levels

Purpose: To investigate the efficacy of N-acetylcysteine as an adjuvant therapy in chronic obstructive pulmonary disease (COPD) with pulmonary interstitial fibrosis (PIF), and its effect on inflammatory factors and serum vascular endothelial growth factor (VEGF) levels. Methods: A total of 94 patients with COPD-PIF from May 2020 to May 2022 in Wuhan Fourth Hospital, China were equally randomized into study and control groups. Control group was administered conventional treatment while the study group was given N-acetylcysteine in addition to conventional treatment. Therapeutic efficacy, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, blood gas, pulmonary fibrosis, and oxidative stress were evaluated. Changes in inflammatory factors, serum vascular endothelial growth factor (VEGF), and incidence of adverse drug reactions were compared. Results: The study group showed significantly higher efficacy, FEV1, FVC, FEV1/FVC compared to control group (p < 0.05). Also, study group showed significantly higher partial pressure of oxygen (PaO2), blood oxygen saturation, superoxide dismutase (SOD), and glutathione (GSH) levels after treatment compared to control group (p < 0.05). Platelet-derived growth factor (PDGF), transforming growth factor (TGF-β), vascular cell adhesion molecule (VCAM), tumor necrosis factor (TNF), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) levels after treatment were significantly lower in the study group than in the control group (p < 0.05). Conclusion: N-acetylcysteine as an adjuvant therapy for COPD-IF is highly effective, improves lung function and oxidative stress, reduces airway inflammation, and VEGF, and attenuates the degree of hypoxia and pulmonary fibrosis with no serious adverse effects. A larger sample size, multicenter, randomized trials to validate these findings and evaluate the downstream regulatory mechanism of Nacetylcysteine in COPD-PIF.

Effect of Kangfuxin liquid combined with triamcinolone acetonide in oral submucosal fibrous degeneration

Purpose: To investigate the effect of Kangfuxin liquid combined with triamcinolone acetonide in the treatment of oral submucous fibrous degeneration. Methods: A total of 140 patients with oral submucosal fibrous degeneration admitted to the outpatient clinic of Haiyan County Stomatological Hospital, China from June 2020 to June 2023 were divided equally into study and control groups. The study group received Kangfuxin liquid in addition to 1 mL triamcinolone acetonide (40 mg/mL) while the control group received 1 mL triamcinolone acetonide; therapeutic effects were compared after 4 weeks of treatment. Visual analogue scale (VAS) score, serum transforming growth factor (TGF-β1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were determined. Also, whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR), and incidence of adverse reactions were evaluated. Result: The study group showed significantly reduced pain levels compared to the control group, as well as lower mucosal damage areas and improved mouth opening after 4 weeks of treatment compared to control group (p < 0.05). Also, the study group showed significantly lower TGF-β1, TNF-α and IL-6 compared to control group after treatment (p < 0.05). It showed significantly lower WBV, PV, and ESR compared to control group (p < 0.05). Furthermore, the study group showed significantly lower incidence of adverse reactions than the control group (p < 0.05). Conclusion: Kangfuxin liquid, when combined with triamcinolone acetonide, lowers pain, reduces the levels of STGF-β1, improves hemorheology, and produces minimal adverse effects compared to triamcinolone alone. Future studies should focus on long-term outcomes to better assess the therapeutic potential of this combined regimen.

The therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on chemically induced atopic dermatitis

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. However, it is still urgent to develop innovative treatments that can effectively manage refractory patients with unpredictable chronic disease courses. In this study, we evaluated the therapeutic efficacy of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a novel agent for AD treatment using a human-like mouse model of AD. PLAG significantly improved 2,4-dinitrochlorobenzene (DNCB)-induced AD skin lesions compared to those in mice treated with DNCB alone. PLAG substantially modulated the AD-induced infiltration of monocytes and eosinophils into skin lesions and humoral systemic responses involving immunoglobulin E (IgE), interleukin (IL)-4, and IL-13, restoring them to a normal state. Next, we compared the therapeutic efficacy of PLAG and abrocitinib for severe AD treatment. PLAG exhibited a significant therapeutic effect on AD skin lesions compared to abrocitinib. Unlike abrocitinib, PLAG significantly reduced AD-induced eosinophil infiltration to a level similar to that observed in untreated negative controls. Notably, both PLAG and abrocitinib downregulated IgE, IL-4, and IL-13 in a similar pattern, reaching levels similar to those in the untreated negative controls. Our findings strongly suggest that PLAG may serve as a therapeutic agent for AD with an efficacy comparable to that of abrocitinib.

Impact of asprosin, interleukin-6, and adiponectin on exocrine pancreatic insufficiency in patients with type 2 diabetes mellitus and chronic pancreatitis

Exocrine pancreatic insufficiency (EPI) is a clinical condition often associated with chronic pancreatitis (CP) and type 2 diabetes mellitus (T2DM) leads to malabsorption and nutritional deficiencies, severely impacting patients’ quality of life. It has been identified that asprosin, a glucogenic protein, is a key player in carbohydrate metabolism and chronic inflammation. Elevated levels of asprosin, along with changes in interleukin‑6 (IL‑6) and adiponectin, may contribute to the pathophysiology of EPI in patients with T2DM and CP. Objective — to investigate the levels of asprosin, IL‑6, and adiponectin and their correlation with exocrine pancreatic function in patients with T2DM and CP. Materials and methods. The study included 100 patients treated at Kharkiv Regional Clinical Hospital from 2020 to 2022. Patients were divided into two groups: Group 1 (n=70) with comorbid T2DM and CP, and Group 2 (n=30) with T2DM alone. The control group included 20 healthy individuals. Blood levels of asprosin, IL‑6, and adiponectin were measured using immunoassays. Fecal elastase‑1 (FE‑1) levels were used to assess exocrine pancreatic function. Pearson’s correlation coefficient was calculated to determine the relationships between these markers. Results. Asprosin levels were significantly higher in Group 1 compared to Group 2 and the control group, with the highest levels observed in patients with comorbid T2DM and CP (10.06±3.56 ng/ml). IL‑6 levels were also elevated in Group 1 (64.44±4.35 pg/ ml), indicating heightened inflammation. Adiponectin levels were lower in Group 1 (2.80±0.38 ng/ml), correlating with worse metabolic profiles. FE‑1 levels were markedly reduced in Group 1 (142.2±6.3 mg/ g), confirming severe EPI. Significant correlations were found between asprosin levels and IL‑6 (positive correlation, r=0.49, p<0.01), as well as between asprosin levels and FE‑1 (negative correlation, r=–0.52, p<0.01). In the group of patients with isolated T2DM, significant moderate negative correlations were found between asprosin levels and adiponectin (r=–0.47, p<0.05) and FE‑1 (r=–0.44, p<0.05). The study also demonstrated a strong negative correlation between adiponectin and IL‑6 (r=–0.61, p<0.01) in patients with comorbid T2DM and CP. Conclusions. Elevated asprosin levels in patients with T2DM and CP are associated with increased inflammation and reduced exocrine pancreatic function. The significant correlations between asprosin, IL‑6, and FE‑1 suggest that asprosin could serve as a clinically valuable biomarker for assessing metabolic and inflammatory status in these patients. The findings highlight the complex interaction between metabolic and inflammatory pathways in the development of EPI.

The association of systemic inflammatory biomarkers with metabolic dysfunction-associated steatotic liver disease and arterial hypertension

Objective — to explore the relationship between metabolic dysfunction‑associated steatotic liver disease (MASLD) on the background of arterial hypertension (AH) and blood inflammatory markers including C‑reactive protein (CRP), Interleukin‑6 (IL‑6), IL‑4, haptoglobin and pentraxin‑3 (PTX‑3). Materials and methods. We examined 102 patients with MASLD. They were divided into 3 groups: group A included 52 patients with isolated MASLD, group B — 23 patients with MASLD and AH stage I, and group C — 27 patients with MASLD and AH stage II. The control group (group D) comprised 20 apparently healthy people. Patients with viral hepatitis, liver cirrhosis, alcoholic liver disease, and AH stage III were excluded. Systemic inflammatory biomarkers analyses were performed using electrochemiluminescence, immunoenzymatic, and immunoturbidimetry techniques. Results. The systemic inflammatory biomarkers analyses revealed significantly higher levels of CRP (p=0.001), IL‑6 (p=0.01), haptoglobin (p<0.05) and PTX‑3 (p<0.01) and decreased levels of IL‑4 (p<0.05) in group B and group C in comparison with the group A and control group (p1 <0.01, p2=0.01). Also, there was a significant increase of CRP (p=0.01), IL‑6 (p=0.01), and PTX‑3 levels (p<0.05) in group B compared with group C. However, the relationship between the IL‑4 (p>0.05) and haptoglobin (p>0.05) levels and the progression of the AH stages have not been confirmed in our study. Conclusions. Our findings indicate the direct relationship between the systemic inflammatory biomarkers’ involvement in developing liver tissue inflammation and the further progression of MASLD. The obtained data indicate the relationship of AH and its stages with the development of chronic systemic inflammatory response in patients with MASLD and AH comorbid course.

Nigella sativa oil attenuates inflammation and oxidative stress in experimental myocardial infarction.

A growing interest in using Nigella sativa oil (NSO) in the prevention or treatment of several cardiovascular diseases has prompted this study. The research aims to investigate the effect of NSO on cardiac damage prevention after long-term administration in induced myocardial infarction (MI) in rats. NSO was analyzed for its fatty acids composition using gas chromatography-mass spectrometry (GC-MS) analysis and administered in rats before and after isoproterenol (45mg/kg body weight) induced myocardial infarction. The following parameters were assessed: electrocardiograms, histopathological examination, serum biochemical aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase-myocardial band (CK-MB), serum and heart inflammation (tumor necrosis factor-alpha (TNF), interleukin 1 beta (IL-1b), and interleukin 6 (IL-6)), and tissue oxidative stress (total antioxidant capacity (TAC), total oxidative stress (TOS), nitric oxide (NO), malondialdehyde (MDA), and the total thiols (THIOL)). Linoleic acid (C18:2n-6) and oleic acid (C18:1n-9) were approximately 89% of total fatty acids while palmitic acid (C16:0) was 6.10%. Administration of NSO for 28 days helped in preventing QT and QTc interval prolongation and reduced heart rate (HR), after MI induction. The histological assessment showed improvement in myofibrillary degeneration and necrosis and also better reduced inflammatory process in the groups treated with NSO. In serum, pro-inflammatory cytokines IL-1b and IL-6 were downregulated in chronic conditions (for IL-1b, NSO vs. control was 86.09vs 150.39 pg/mL, and for IL-6 NSO vs. control was 78.00 vs. 184.98 pg/ml). In the heart tissue, the downregulation was observed only for TNF in both acute and chronic conditions (acute NSO vs. control was 132.37 vs. 207.63 pg/mL, and chronic NSO vs. control was 135.83 vs. 183.29 pg/ml). The pro-oxidant parameters TOS, NO, MDA, and OSI, were reduced in the groups treated with NSO only after 14 days of treatment, suggesting that the NSO antioxidant effect is time-dependent. NSO administration might have a favourable impact on the regulation of oxidative stress and inflammation processes after MI induction in rats, and it is worth considering its administration as an adjuvant treatment.

USP15 inhibits hypoxia-induced IL-6 signaling by deubiquitinating and stabilizing MeCP2.

Methyl-CpG binding protein 2 (MeCP2) is an important X-linked DNA methylation reader and a key heterochromatin organizer. The expression level of MeCP2 is crucial, as indicated by the observation that loss-of-function mutations of MECP2 cause Rett syndrome, whereas an extra copy spanning the MECP2 locus results in MECP2 duplication syndrome, both being progressive neurodevelopmental disorders. Our previous study demonstrated that MeCP2 protein expression is rapidly induced by renal ischemia-reperfusion injury (IRI) and protects the kidney from IRI through transcriptionally repressing the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 signaling pathway. However, the mechanisms underlying the upregulation of MeCP2 have remained elusive. Here, by using two hypoxia cell models, hypoxia and reoxygenation and cobalt chloride stimulation, we confirmed that the removal of lysine 48-linked ubiquitination from MeCP2 prevented its proteasome-dependent degradation under hypoxic conditions. Through unbiased screening based on a deubiquitinating enzymes library, we identified ubiquitin-specific protease 15 (USP15) as a stabilizer of MeCP2. Further studies revealed that USP15 could attenuate hypoxia-induced MeCP2 degradation by cleaving lysine 48-linked ubiquitin chains from MeCP2, primarily targeting its C-terminal domain. Consistently, USP15 inhibited hypoxia-induced signal transducer and activator of transcription 3 activation, resulting in reduced transcription of IL-6 downstream genes. In summary, our study reveals an important role for USP15 in the maintenance of MeCP2 stability and the regulation of IL-6 signaling.

The use of interleukin-10 (IL-10) and phosphorus levels as predictors of the time to improvement in COVID-19 patients: a prospective study

Early detection of COVID-19 improves the chance of recovery and helps identify high-risk patients. Our study aimed to statistically predict the time to improvement with the admission data of COVID-19 patients.Methods: Our prospective cohort study occurred between January and September 2022 at Alexandria University Hospital’s outpatient clinic and isolation department. We enrolled 43 patients after assessing their eligibility and collecting their baseline data.Results: The mean age was 34.8 years (± 12.3). Most of them were females (65.1%). The mean of oxygen saturation was 95.2% (± 2.8). We used linear regression to predict how long it would take to improve [time to improvement (days) = 1.186*P (mmol/L) + 0.010*IL-10 (pg/mL)]. Its diagnostic performance was 0.723 (95% CI: 0.552–0.894), and it was accurate at predicting improvement within a week but not at longer delays; additionally, its positive and negative predictive values were 56.3% and 85.2%, respectively.Conclusion: We recommend monitoring phosphorus and interleukin-10 levels. The time-to-improvement delay negatively correlated with a reduction in baseline oxygen saturation upon admission. Additionally, for every 0.84 meq/L increase in phosphorus or 100 pg/mL increase in interleukin-10, there was a 1-day delay provided that the other was constant, with a coefficient of determination of 85.9%.

The Role of Interleukin-24 and Downstream Pathways in Inflammatory and Autoimmune Diseases.

Inflammatory and autoimmune diseases are pathological immune disorders and pose significant public health challenges due to their impact on individuals and society. Cytokine dysregulation plays a critical role in the development of these disorders. Interleukin (IL)-24, a member of the IL-10 cytokine family, can be secreted by various cell types, including immune and non-immune cells. The downstream effects of IL-24 upon binding to its receptors can occur in dependence on, or independently of, the Janus kinase (JAK)/signal transducer and the activator of transcription (STAT) signaling pathway. IL-24 and its downstream pathways influence crucial processes such as cell differentiation, proliferation, apoptosis, and inflammation, with its role varying across different diseases. On the one hand, IL-24 can inhibit the activation of pathogenic cells and autoimmune responses in autoimmune ocular diseases; on the other hand, IL-24 has been also implicated in promoting tissue damage by fostering immune cell activation and infiltration in psoriasis and allergic diseases. It suggests that IL-24, as a multifunctional cytokine, has complex regulatory functions in immune cells and related diseases. In this paper, we summarize the current knowledge on IL-24's immunomodulatory actions and its involvement in inflammatory and autoimmune disorders. Such insights may pave the way for novel therapeutic strategies for these diseases.

Identification of novel cytokine to judge the diagnosis and clinical phenotype of adult-onset Still’s disease

This study aimed to identify biomarkers to distinguish adult-onset Still’s disease (AOSD) and to predict disease phenotypes. In total, 49 patients diagnosed with AOSD and 200 patients with common diseases (controls) were included in the analysis. The levels of 69 cytokines were analyzed using a multi-suspension cytokine array. Cytokine cluster analysis was performed to identify specific molecular networks. Furthermore, random forest analysis and logistic regression analysis were used to rank cytokines based on their importance and to determine specific biomarkers for identification of AOSD patients and phenotypes. Patients with AOSD demonstrated significantly higher macrophage migration inhibitory factor (MIF) and interleukin (IL)-12(p40) serum levels than controls and patients with rheumatoid arthritis. Serum levels of chemokine (C-C motif) ligand (CCL) 8 and CCL22 were significantly lower in AOSD patients with a polycyclic systemic disease phenotype and could be differentiated with high accuracy from the other phenotypes (cutoff value for CCL8 = 122.7 pg/mL, CCL22 = 593.3 pg/mL, sensitivity 66.7%, specificity 87.1%, area under the curve 0.843). Combined MIF and IL-12(p40) levels may represent a biomarker for differentiating patients with AOSD from those with other diseases. The chemokine profiles of AOSD with a polycyclic systemic disease phenotype may differ from other phenotypes.

Features of subset composition and functional activity of blood lymphocytes in tick-borne infections of different etiologies

Aim. To perform a comparative assessment of subset composition and functional activity of peripheral blood lymphocytes in patients with tick-borne encephalitis (TBE) and ixodid tick-borne borreliosis (ITBB) in the acute phase of the disease.Materials and methods. The study involved 22 patients with febrile and meningeal TBE, 15 patients with ITBB with and without erythema, and 11 healthy controls. Subset composition of blood lymphocytes was determined by flow cytometry. The blast transformation assay was applied to assess lymphocyte proliferation. Cytokine-producing activity of cells was studied in 24-hour incubated mononuclear cell cultures. Cytokine concentrations (interleukin (IL)-2, IL-4, IL-10, interferon (IFN)γ) were determined in the supernatants by the enzyme-linked immunosorbent assay (ELISA).Results. Patients with TBE demonstrated an increase in the proportion of helper – inducer T-cells, a pronounced decrease in the proportion and absolute count of cytotoxic T cells, and low T lymphocyte count compared to the control values. The study in ITBB patients revealed an increase in the helper – inducer T-cell count and the proportion of NK-cells, a decrease in the cytotoxic T cell count, and the T lymphocyte count comparable to normal values. The most significant decrease in the levels of phytohemagglutinin-induced lymphocyte proliferation was found in patients with TBE. Patients of both groups showed a decrease in IL-2 secretion in the mononuclear cell culture, a rise in IL-4 and IL-10 production, and IFNγ production levels comparable to control values.Conclusion. The study of TBE patients revealed relative lymphocytopenia with changes in the subset composition of lymphocytes characterized by an increase in the proportion of helper – inducer T-cells and a decrease in the absolute cytotoxic T lymphocyte count. Patients with ITBB demonstrated an increase in the proportion of NK-cells and a more pronounced imbalance in the T-helper / cytotoxic T lymphocyte ratio. Changes in the functional phenotype of lymphocytes, regardless of the etiology of tick-borne infection, were characterized by reduced proliferative reserve, low IL-2 secretion, increased IL-4 and IL-10 production, and depressed reactivity of lymphocytes with respect to IFNγ secretion.

Assessment of IV albumin and ringer lactate on the acute oral toxicity of acetylsalicylic acid in albino rats

BackgroundDespite the frequent inclusion of fluid therapy in the treatment of many conditions, there are limited studies available to provide an evidence-based specific recommendation for fluid therapy in acute drug toxicity. Salicylate toxicity is considered one of the common clinical problems. It is commonly associated with fatal complications and even can lead to death. The study was designed to investigate the effects of various IV fluid types as isotonic saline (NaCl 0.9%), Ringer lactate (RL), and albumin and their impact on acetyl salicylic acid (ASA) toxicity outcome in a rat model of acute salicylate toxicity.Sixty male Albino rats were divided into 10 groups of 6 rats each. The first four groups were the control, saline, RL, and albumin groups. The fifth group received two doses of ASA solution orally, and the next five groups were treated with IV fluids as follows: saline-ASA, RL-ASA, albumin-ASA, RL + albumin-ASA, and saline + albumin-ASA. Upon completion of the study, spirometry, arterial blood gas analysis (ABG), and serum liver and kidney function tests were done on all groups. Furthermore, quantitative real-time polymerase chain reaction (PCR) was used to assess interleukin-6 (IL6), nuclear factor kappa beta (NF-kβ), and beta-actin mRNA gene expression of histopathology and immunohistochemistry assessments were also performed on liver and kidney tissues.ResultsThe results revealed the ASA group showed marked deterioration across all the investigated parameters. The groups that received saline and RL showed improvements in the following: respiratory rates, ABG, liver and kidney function, and histopathological findings.The RL + albumin group did not show any improvements. The albumin group and the saline + albumin group showed variable responses, ranging from mild improvement to no improvement.ConclusionsThe saline and RL groups showed positive results; however, the RL + albumin group showed the worst outcomes. The inclusion of albumin did not appear to provide any extra benefits and produced varying results.

Yoga Intervention and Inflammatory Homoeostasis in Breast Cancer Patients

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

Clinical and molecular factors associated with external apical root resorption by orthodontics: Umbrella review

The objective of this study was to analyze the available evidence on external apical root resorption (EARR) due to orthodontic movement to identify clinical and molecular factors associated with this condition. An umbrella review that included systematic reviews and meta-analysis was performed. Four databases were used (PubMed, Science Direct, Scopus, and Cochrane), and critical evaluation following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and admeasurement tool to assess systematic reviews (AMSTAR-2) guidelines were carried out. The study protocol was registered in PROSPERO (International prospective register of systematic reviews, CRD42020198971). One hundred and twenty-four papers were eligible for this investigation. After exclusion by title and abstract, 10 papers (four systematic reviews and six meta-analyses) were included in the study. Guideline AMSTAR-2 was applied, and evaluation was performed using the PRISMA guideline. Factors such as female gender, adulthood, conventional fixed orthodontic treatment, heavy, continuous, and prolonged loads, intrusive movements, and anterior superior teeth with abnormal roots increase the risk of developing this condition. At the molecular level, some biomarkers, such as interleukins (IL) I-1B, I-6, I-4, and dentin phosphoprotein, are significant to reach an early diagnosis of external root resorption (ERR), especially the gene of polymorphism IL-1B (+3954), which is the most important predictor of this condition in patients under orthodontic treatment. Clinical and molecular factors respond to individual characteristics that must be identified to define the risk of developing EARR. Cone-beam computed tomography is the most accurate tool to evaluate the dimension of this condition. Prolonged treatments must be avoided, and immunoassays to analyze proteins in the gingival crevicular fluid should be included to reach an early diagnosis.

Spesolimab, the first-in-class anti-IL-36R antibody: From bench to clinic.

Inflammatory diseases that are driven by several pro-inflammatory cytokines has resulted in in the development of targeted therapies across different disease settings. Interleukin (IL)-36 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL-36 receptor (IL-36R)-targeting antibody, spesolimab, in IL-36-mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL-36R at a binding site distinct from its agonists, IL-36α/β/γ, and at least one endogenous antagonist, IL-36R antagonist. Invitro and invivo data for spesolimab show effective inhibition of IL-36R-mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL-36R-mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient-reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL-36 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL-36 in the human immune system and the mechanism behind IL-36-mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need.