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1.
Front Endocrinol (Lausanne) ; 14: 1255925, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37867523

RESUMO

Objective: Increased inflammation and cytokine levels are considered risk factors and promoters of preterm birth (PTB). However, the regulatory mechanism of pregnancy-related inflammation remains unclear. Toll-like receptor 4 (TLR4) plays a critical role in inflammatory responses in various diseases. Therefore, our study aimed to investigate whether TLR4 is involved in the inflammatory responses during uterine activation for labor, with the goal of identifying potential biomarkers for uterine activation at term. Materials and methods: We used flow cytometry to detect TLR4 expression on CD14+ maternal blood monocytes in the first, second, and third trimesters. ELISA was employed to measure TLR4 and cytokines levels in the maternal serum of term non-labor (TNL), term labor (TL) women and LPS induced preterm labor and PBS injected controls. TLR4siRNA was transfected into the human myometrial smooth muscle cells (HMSMCs), which were subsequently treated with IL-1ß. The mRNA and protein levels of TLR4, uterine contraction-related protein connexin 43 (CX43), oxytocin receptor (OTR), MAPK/NF-κB signaling pathway, and cytokines were analyzed using qRT-PCR, western blotting, and immunohistochemistry. Results: The study revealed TLR4 expression on CD14+ maternal blood monocytes was higher in the third trimester group compared to the first and second trimester groups (p<0.001). Maternal serum concentrations of TLR4 and cytokines were significantly higher in the TL group than the TNL group (p<0.001). TLR4, OTR, CX43, activated MAPK/NF-κB expression, and cytokines levels were upregulated in TL group, and similarly significantly higher in the LPS-induced preterm group than in the control group. Using the HMSMCs we demonstrated that TLR4siRNA transfection suppressed contractility. Interfering with TLR4 expression reduced the expression of OTR, CX43, cytokines, and MAPK/NF-κB activation. There was a significant positive relationship between TLR4 expression and the inflammatory status in the myometrium. ROC analysis indicated that TLR4 and cytokines may serve as potential biomarkers for predicting uterine activation for labor. Conclusion: Our data suggest that TLR4 and cytokines can act as stimulators of uterine activation for labor at term. Furthermore, the MAPK/NF-κB pathway appears to be one of the potential signaling pathways mediating TLR4's regulation of parturition initiation.


Assuntos
Miométrio , Nascimento Prematuro , Feminino , Humanos , Gravidez , Biomarcadores/sangue , Biomarcadores/metabolismo , Conexina 43/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Inflamação/metabolismo , NF-kappa B/metabolismo , Nascimento Prematuro/metabolismo , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/metabolismo
2.
Front Immunol ; 14: 1222170, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483627

RESUMO

Background: The severity of COVID-19 is associated with an elevated level of a variety of inflammatory mediators. Increasing evidence suggests that the Th17 response contributes to the severity of COVID-19 pneumonia, whereas Th22 response plays a regulatory role in SARS-CoV-2 infection. Two main types of available COVID-19 treatments are antivirals and immunomodulatory drugs; however, their effect on a cytokine profile is yet to be determined. Methods: This study aim to analyse a cytokine profile in peripheral blood from patients with COVID-19 (n=44) undergoing antiviral or/and immunomodulatory treatment and healthy controls (n=20). Circulating CD4+ and CD8+ T cells and their intracellular expression of IL-17A and IL-22 were assessed by flow cytometry. Results: Initial results showed an overexpression of IL-17F, IL-17A, CCL5/RANTES, GM-CSF, IL-4, IL-10, CXCL-10/IP-10 and IL-6 in COVID-19 patients compared to healthy controls. Treatment with remdesivir resulted in a significant decline in concentrations of IL-6, IL-10, IFN-alpha and CXCL10/IP-10. Immunomodulatory treatment contributed to a significant downregulation of IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 as well as upregulation of IL-22 and IL-1 beta. A combination of an antiviral and immunomodulatory treatment resulted in a significant decrease in IL-17F, IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 levels as well as an increase in IL-17A and IL-1 beta. We found significantly higher percentage of both CD4+ and CD8+ T cells producing IL-17A and CD4+ T cells producing IL-22 in patients with COVID-19. Conclusion: Administration of antiviral or/and immunomodulatory treatment resulted in a significant downregulation of pro-inflammatory cytokine expression and an upregulation of T cell absolute counts in most cases, thus showing effectiveness of treatment in COVID-19. SARS-CoV-2 infection induced cytokine overexpression in hospitalized patients with COVID-19 as well as lymphopenia, particularly a decrease in CD4+ and CD8+ T cell counts. Moreover, despite the reduced counts of CD4+ and CD8+ T cells, both subsets showed overactivation and increased expression of IL-17A and IL-22, thus targeting Th17 response might alleviate inflammatory response in severe disease.


Assuntos
Antivirais , COVID-19 , Citocinas , Agentes de Imunomodulação , Interleucinas , Antivirais/uso terapêutico , Agentes de Imunomodulação/uso terapêutico , Humanos , COVID-19/sangue , COVID-19/diagnóstico , Estudos de Casos e Controles , Citocinas/sangue , Citocinas/efeitos dos fármacos , Interleucina-17/metabolismo , Interleucinas/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso
3.
Discov Med ; 35(176): 343-352, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37272101

RESUMO

BACKGROUND: Immune dysregulation contributes to the development of ulcerative colitis (UC). The research on the inflammatory response of UC is mainly focused on T cells, with less understanding of the role of B cells. Pax transactivation domain-interacting protein (PTIP) is essential for the development of B cell subpopulations and humoral immunity. The purpose of this study was to elucidate the role of PTIP in B cells of mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: The B-cell-specific PTIP knockout (PTIP-/-) mice were established by crossbreeding cluster of differentiation (CD)19cre/cre mice with PTIPflox/flox mice. The UC mice were induced by drinking water supplemented with 3.8% Dextran Sulfate Sodium (DSS) (PTIP-/- + DSS). The histological analysis was performed using hematoxylin and eosin staining. The immune cells were isolated using a fluorescence-activated cell sorter. The serum antibodies (immunoglobulin M (IgM) or immunoglobulin G (IgG)) and tumor necrosis factor (TNF)-α were determined by Enzyme linked immunosorbent assay (ELISA). RESULTS: Interestingly, our findings demonstrate that PTIP deficiency in B cells significantly ameliorates UC. In contrast to PTIP-/- + DSS, the wild type (WT) + DSS group showed a more robust increase in disease activity index (DAI) scores (p < 0.05), a substantially shortened colon (p < 0.001) and a decrease of mucous-producing goblet cells and the complete destruction of crypts. Moreover, PTIP-deficient mice manifested markedly altered neutrophil and T-cell distribution in UC (p < 0.05). Although anti-commensal IgG exacerbates UC, we demonstrated, for the first time, that serum natural IgG does not aggravate the pathology of UC. Furthermore, PTIP regulates UC by controlling B-2 cells independently from T cells. CONCLUSIONS: Transplantation of splenic B-2 cells from PTIP-deficient mice protected recipient NOD/ShiltJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mice from severe UC.


Assuntos
Colite Ulcerativa , Proteínas de Ligação a DNA , Animais , Camundongos , Colite Ulcerativa/sangue , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Sulfato de Dextrana , Linfócitos B/citologia , Citocinas/sangue
4.
Cytokine ; 169: 156280, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37356260

RESUMO

OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.


Assuntos
Citocinas , Síndrome de Linfonodos Mucocutâneos , Choque Séptico , Síndrome de Resposta Inflamatória Sistêmica , Infecções por Yersinia pseudotuberculosis , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Citocinas/sangue , Humanos , Interleucina-6/sangue , Quimiocina CXCL9/sangue , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Choque Séptico/sangue , Choque Séptico/diagnóstico , Infecções por Yersinia pseudotuberculosis/sangue , Infecções por Yersinia pseudotuberculosis/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
5.
BMC Pregnancy Childbirth ; 23(1): 460, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344822

RESUMO

OBJECTIVE: To evaluate the association between second trimester plasma cytokine levels in asymptomatic pregnant women and preterm births (PTB) in an attempt to identify a possible predictor of preterm birth. METHODS: The study design was a nested case-control study including women with singleton a gestational age between 20-25(+ 6) weeks from two Brazilian cities. The patients were interviewed, Venous blood samples were collected. The participants were again evaluated at birth. A total of 197 women with PTB comprised the case group. The control group was selected among term births (426 patients). Forty-one cytokines were compared between groups. RESULTS: When only spontaneous PTB were analyzed, GRO, sCD40L and MCP-1 levels were lower in the case group (p < 0.05). Logarithmic transformation was performed for cytokines with discrepant results, which showed increased levels of IL-2 in the group of spontaneous PTB (p < 0.05). In both analyses, the incidence of maternal smoking and of a history of preterm delivery differed significantly between the case and control groups. In multivariate analysis, only serum GRO levels differed between the case and control groups. CONCLUSION: Lower second trimester serum levels of GRO in asymptomatic women are associated with a larger number of PTB. This finding may reflect a deficient maternal inflammatory response.


Assuntos
Citocinas , Nascimento Prematuro , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos de Casos e Controles , Citocinas/sangue , Segundo Trimestre da Gravidez , Nascimento Prematuro/etiologia , Fatores de Risco , Nascimento a Termo
6.
Crit Care ; 27(1): 215, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259160

RESUMO

INTRODUCTION: Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings. METHODS: We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010-29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334). RESULTS: Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias. INTERPRETATION: To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.


Assuntos
Adsorção , Ponte Cardiopulmonar , Citocinas , Citocinas/efeitos adversos , Citocinas/sangue , Citocinas/metabolismo , Cirurgia Torácica , Complicações Pós-Operatórias/prevenção & controle
7.
Gynecol Endocrinol ; 39(1): 2217290, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37236244

RESUMO

OBJECTIVE: To investigate the efficacy of new endometriosis biomarkers in diagnosis and treatment. METHODS: Thirty women with Stage III-IV endometriosis who were given an indication for surgery and 49 control patients were compared. Preoperative and postoperative serum levels of Annexin A5 (ANXA5), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble vascular cell adhesion molecule-1 (sVCAM-1), vascular endothelial growth factors (VEGF) and Ca-125 measurements were compared. RESULTS: AUCs of ANXA5, sICAM-1, IL-6, TNF-α, VCAM-1, VEGF biomarkers were not found to be significant in diagnosing endometriosis when evaluated alone (p > 0.05). Only the AUC of the Ca-125 biomarker values were found to be significant with 73% sensitivity and 98% specificity (p < 0.001). However, when Ca-125 and ANXA5 were evaluated together, it was concluded that the diagnosis of endometriosis could be made with 73% sensitivity and 100% specificity. CONCLUSION: When Ca-125 and ANXA5 are evaluated together, it seems to be more valuable than Ca-125 alone in diagnosing endometriosis.


Assuntos
Biomarcadores , Citocinas , Endometriose , Feminino , Humanos , Biomarcadores/sangue , Antígeno Ca-125 , Endometriose/metabolismo , Interleucina-6 , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular , Fator A de Crescimento do Endotélio Vascular , Estudos de Casos e Controles , Citocinas/sangue
8.
Biochem Genet ; 61(6): 2276-2292, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37020118

RESUMO

The anti-inflammatory adipokine intelectin-1, which is encoded by the ITLN1 gene, is hypothesized to be linked to the pathogenesis of type 2 diabetes (T2DM) and obesity. The purpose of this study was to examine the effect of the ITLN1 gene polymorphism rs2274907 on obesity and T2DM in Turkish adults. The impact of genotype on lipid profiles and serum intelectin levels in the obese and diabetes groups was also investigated. Randomly selected 2266 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish adult risk factor study were cross-sectionally analyzed. The genotyping of rs2274907 A > T polymorphism was performed by using the hybridization probe based LightSNiP assay in real-time PCR. T2DM were defined using the criteria of the American Diabetes Association. Obesity was described as Body mass index ≥ 30 kg/m2. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements. According to findings, there was no vital connection between the rs2274907 polymorphism and obesity, T2DM, or serum intelectin-1 level. The TA+AA carriers had significantly higher triglyceride levels (p = 0.007) compared with the TT carriers in both obese and T2DM women when adjusted for relevant covariates. ITLN1 rs2274907 polymorphism is not correlated with the risk of obesity and T2DM and not affect serum ITLN1 levels in Turkish adults. However, this polymorphism appears to be important in regulating triglyceride levels in obese and diabetic women.


Assuntos
Diabetes Mellitus Tipo 2 , Lectinas , Obesidade , Humanos , Obesidade/genética , Diabetes Mellitus Tipo 2/genética , Lipídeos/sangue , Lectinas/sangue , Lectinas/genética , Citocinas/sangue , Citocinas/genética , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/genética , Fatores de Risco , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Genótipo , Frequência do Gene
9.
BMC Ophthalmol ; 23(1): 141, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37020269

RESUMO

BACKGROUND: To evaluate the aqueous humor (AH) levels of cytokines in primary open-angle glaucoma (POAG) patients and cataract patients. METHODS: Thirty-eight POAG patients and 26 cataract patients were recruited. Peripheral blood (PB) was collected from each subject. The POAG group was divided into 2 subgroups according to the severity of visual field defects. The cutoff point of the mean deviation (MD) of the visual field was -12 dB. AH was obtained at the time of anterior chamber puncture during cataract or glaucoma surgery by using a 27-gauge needle attached to a microsyringe. AH and PB levels of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta2 (TGF-ß2) and IL-4 were assayed by enzyme-linked immunosorbent assay. Postoperative intraocular pressures (IOPs) of POAG patients were recorded during the follow-up period. RESULTS: TNF-α and TGF-ß2 showed significantly higher AH levels in the POAG group than in the cataract group (P < 0.001 and P = 0.001, respectively). For the POAG group, preoperative IOPs were significantly positively correlated with AH levels of TNF-α (r2 = 0.129, P = 0.027) and TGF-ß2 (r2 = 0.273, P = 0.001). AH levels of TGF-ß2 were significantly different among cataract patients, POAG patients with MD> -12 dB and POAG patients with MD≤ -12 dB (P = 0.001). AH levels of TNF-α were significantly positively associated with IOP reduction after trabeculectomy (P = 0.025). AH and PB levels of cytokines were not related to the long-term success of trabeculectomy. CONCLUSION: The levels of TNF-α and TGF-ß2 showed different profiles in POAG patients and cataract patients. AH levels of TGF-ß2 were correlated with the severity of glaucomatous neuropathy in POAG patients. The findings suggest possible roles for cytokines in the pathogenesis and development of POAG.


Assuntos
Humor Aquoso , Catarata , Citocinas , Glaucoma de Ângulo Aberto , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Campos Visuais , Humor Aquoso/metabolismo , Citocinas/sangue , Pressão Intraocular , Interleucina-2/sangue , Interleucina-4/sangue , Fator de Crescimento Transformador beta2/sangue , Fator de Necrose Tumoral alfa/sangue , Masculino , Feminino , Pessoa de Meia-Idade
10.
J Microbiol Biotechnol ; 33(6): 823-830, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-36908272

RESUMO

Lactococcus lactis is a lactic acid bacterium and used in the dairy food industry. The ameliorating effects of Lactobacillus species on atopic dermatitis (AD) have been extensively studied, but the specific effect of L. lactis strains has not yet been investigated. In this study, the efficacy of L. lactis LB 1022, isolated from natural cheese, was evaluated using RAW 264.7, HMC-1 and HaCaT cell lines and an ovalbumin-sensitized AD mouse model. L. lactis LB 1022 exhibited nitric oxide suppression and anti-allergy and anti-inflammatory activity in vitro. Oral administration of L. lactis LB 1022 to AD mice significantly reduced the levels of IgE, mast cells, and eosinophils, and a range of T cell-mediated T helper Th1, Th2, and Th17-type cytokines under interleukin (IL)-10, transforming growth factor-ß (TGF-ß), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP). In addition, L. lactis LB 1022 treatment increased the concentration of short-chain fatty acids. Overall, L. lactis LB 1022 significantly modulated AD-like symptoms by altering metabolites and the immune response, illustrating its potential as candidate for use in functional food supplements to alleviate AD.


Assuntos
Dermatite Atópica , Agentes de Imunomodulação , Lactococcus lactis , Animais , Camundongos , Dermatite Atópica/imunologia , Dermatite Atópica/terapia , Células RAW 264.7 , Humanos , Células HaCaT , Anti-Inflamatórios , Citocinas/sangue , Ácidos Graxos Voláteis/metabolismo , Feminino , Camundongos Endogâmicos BALB C , Imunoglobulina E/sangue , Óxido Nítrico/metabolismo , Antialérgicos , Eosinófilos , Mastócitos
11.
Eur J Histochem ; 67(2)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36951266

RESUMO

Acute pancreatitis is an inflammatory response in the pancreas, involving activation of pancreatic enzymes. Severe acute pancreatitis (SAP) often causes systemic complications that affect distant organs, including the lungs. The aim of this study was to explore the therapeutic potential of piperlonguminine on SAP-induced lung injury in rat models. Acute pancreatitis was induced in rats by repetitive injections with 4% sodium taurocholate. Histological examination and biochemical assays were used to assess the severity of lung injury, including tissue damage, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), reactive oxygen species (ROS), and inflammatory cytokines. We found that piperlonguminine significantly ameliorated pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening in rats with SAP. In addition, NOX2, NOX4, ROS, and inflammatory cytokine levels in pulmonary tissues were notably decreased in piperlonguminine-treated rats. Piperlonguminine also attenuated the expression levels of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB). Together, our findings demonstrate for the first time that piperlonguminine can ameliorate acute pancreatitis-induced lung injury via inhibitory modulation of inflammatory responses by suppression of the TLR4/NF-κB signaling pathway.


Assuntos
Lesão Pulmonar , Pancreatite , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , NF-kappa B/metabolismo , Pancreatite/complicações , Pancreatite/metabolismo , Masculino , Animais , Ratos , Ratos Sprague-Dawley , Citocinas/sangue , Transdução de Sinais/efeitos dos fármacos
12.
Vopr Pitan ; 92(1): 55-62, 2023.
Artigo em Russo | MEDLINE | ID: mdl-36883540

RESUMO

One of the main issues of the peculiarities of the immune reactions of the gastrointestinal tract is the mechanisms of ensuring tolerance to food antigens. Concentrations of antibodies to food antigens actually reflect the state of the intestinal mucosa barrier function, and the degree of penetration of antigens into the blood determines the level of immune response to them. The aim of the study was to determine the risk criteria for violation of tolerance to food antigens. Material and methods. The study included the results of a survey and examination of 1334 adults living in the north of the European part of the Russian Federation, including 1100 born in the North, of which 970 were women and 364 were men. The average age of the respondents was 45.5±1.0 years. The comparison group consisted of 344 patients with pathology of the gastrointestinal tract who applied to the medical company "Biocor". The content of immunoglobulins (Ig) G to food antigens, total IgA, cytokines (tumor necrosis factor α, interleukin-6, interleukin-4) in blood serum were determined by enzyme immunoassay. Results. Rural residents often (more than 28%) have elevated concentrations of IgG to potato, river fish, wheat and rye antigens. Urban residents have the most pronounced decrease in tolerance to food antigens of chicken, cod, beef and pork. In healthy individuals, elevated (>100 ME/ml) concentrations of antibodies to meat products are recorded in the range of 11.3-13.9%, to dairy antigens - 11.5-14.1%, cereals - 11.9-13.4%. Slightly less frequently, elevated concentrations of antibodies to fish antigens (7.5-10.1%), vegetables (3.8-7.0%) and fruits (4.9-6.5%) are detected. In inflammatory and oncological diseases of the gastrointestinal tract, the content of antibodies to food antigens increases sharply. On average, the frequency of impaired tolerance to food antigens in patients is 2.7-6.1 times higher than in healthy individuals. Conclusion. Violation of tolerance to food antigens is associated with an increase in blood pro-inflammatory cytokines, mainly interleukin-6. In practically healthy individuals, a decrease in tolerance to food antigens is associated with a deficiency of blood IgA. The risk criteria for violation of the diet or consumption of low-quality foods may be an increase in the frequency of detection of elevated concentrations of antibodies to meat products in 14.6±3.0%, fish - 10.7±2.3%, cereals - 13.7±1.6%, dairy products - 14.8±1.5%, vegetables - 7.8±2.4% and fruits - 6.9±5.8%.


Assuntos
Anticorpos , Antígenos , Alimentos , Tolerância Imunológica , Imunoglobulina A , Interleucina-6 , Feminino , Humanos , Masculino , Citocinas/sangue , Citocinas/imunologia , Grão Comestível , Frutas , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Verduras , Adulto , Pessoa de Meia-Idade , Antígenos/sangue , Antígenos/imunologia , Tolerância Imunológica/imunologia , Anticorpos/sangue , Anticorpos/imunologia , Medição de Risco
13.
Front Immunol ; 14: 1121778, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36756119

RESUMO

Objective: The aim of this study was to explore the profile of cytokine changes during the combination therapy with pegylated interferon alpha (PEG-IFN-α) and its relationship with HBsAg loss in nucleos(t)ide analogs (NAs)-suppressed chronic hepatitis B patients. Methods: Seventy-six patients with chronic hepatitis B with HBsAg less than 1,500 IU/ml and HBV DNA negative after receiving ≥ 1-year NAs therapy were enrolled. Eighteen patients continued to take NAs monotherapy (the NAs group), and 58 patients received combination therapy with NAs and PEG-IFN-α (the Add-on group). The levels of IFNG, IL1B, IL1RN, IL2, IL4, IL6, IL10, IL12A, IL17A, CCL2, CCL3, CCL5, CXCL8, CXCL10, TNF, and CSF2 in peripheral blood during treatment were detected. Results: At week 48, 0.00% (0/18) in the NAs group and 25.86% (15/58) in the Add-on group achieved HBsAg loss. During 48 weeks of combined treatment, there was a transitory increase in the levels of ALT, IL1RN, IL2, and CCL2. Compared to the NAs group, CXCL8 and CXCL10 in the Add-on group remain higher after rising, yet CCL3 showed a continuously increasing trend. Mild and early increases in IL1B, CCL3, IL17A, IL2, IL4, IL6, and CXCL8 were associated with HBsAg loss or decrease >1 log, while sustained high levels of CCL5 and CXCL10 were associated with poor responses to Add-on therapy at week 48. Conclusions: The serum cytokine change profile is closely related to the response to the combination therapy with PEG-IFN-α and NAs, and may help to reveal the mechanism of functional cure and discover new immunological predictors and new therapeutic targets.


Assuntos
Citocinas , Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Interferon-alfa , Humanos , Antivirais/uso terapêutico , Citocinas/sangue , Antígenos E da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucina-2 , Interleucina-4 , Interleucina-6
14.
Transl Psychiatry ; 13(1): 9, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36631451

RESUMO

Immunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1ß, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.


Assuntos
Proteínas do Sistema Complemento , Transtornos Psicóticos , Humanos , Citocinas/sangue , Citocinas/química , Inflamação/metabolismo , Transtornos Psicóticos/sangue , Transtornos Psicóticos/diagnóstico , Fatores de Risco , Fator de Necrose Tumoral alfa , Proteínas do Sistema Complemento/química , Complemento C1q/química , Complemento C3b/química , Complemento C4b/química , Complemento C5b/química
15.
Am Heart J ; 258: 157-167, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36646198

RESUMO

BACKGROUND: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1ß, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF. METHODS: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, education, hypertension, diabetes, hyperlipidemia, current smoking, and history of coronary heart disease, congestive heart failure, or peripheral artery disease. RESULTS: Of 16,729 women, 3,943 developed AF over an average of 8.5 years. Racial and ethnic groups included White (77.4%), Black/African-American (16.1%), Asian (2.7%), American Indian/Alaska Native (1.0%), and Hispanic (5.5%). Baseline IL-1ß log continuous levels were not significantly associated with incident AF (HR 0.86 per 1 log [pg/mL] increase, P= .24), similar to those of other inflammatory cytokines, IL-7, IL-8, IL-10, IGF-1, and TNF-α. There were significant associations between C-reactive protein (CRP) and IL-6 with incident AF. CONCLUSIONS: In this large cohort of postmenopausal women, there was no significant association between IL-1ß and incident AF, although downstream effectors, CRP and IL-6, were associated with incident AF.


Assuntos
Fibrilação Atrial , Interleucina-1beta , Pós-Menopausa , Feminino , Humanos , Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Incidência , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Interleucina-6 , Pós-Menopausa/metabolismo , Modelos de Riscos Proporcionais , Fatores de Risco
16.
J Cancer Surviv ; 17(4): 1082-1093, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36350483

RESUMO

PURPOSE: Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects. METHODS: In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls. RESULTS: Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls. CONCLUSIONS: More than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls. IMPLICATIONS FOR CANCER SURVIVORS: This study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT.


Assuntos
Sobreviventes de Câncer , Citocinas , Transtornos de Deglutição , Síndrome de Fadiga Crônica , Neoplasias de Cabeça e Pescoço , Xerostomia , Neoplasias de Cabeça e Pescoço/radioterapia , Citocinas/sangue , Qualidade de Vida , Xerostomia/sangue , Xerostomia/epidemiologia , Transtornos de Deglutição/sangue , Transtornos de Deglutição/epidemiologia , Estudos Transversais , Humanos , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/epidemiologia , Prevalência , Inquéritos e Questionários , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso
17.
Med Sci Sports Exerc ; 55(3): 548-557, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563092

RESUMO

PURPOSE: Initial military training (IMT) is a transitionary period wherein immune function may be suppressed and infection risk heightened due to physical and psychological stress, communal living, and sleep deprivation. This study characterized changes in biomarkers of innate and adaptive immune function, and potential modulators of those changes, in military recruits during IMT. METHODS: Peripheral leukocyte distribution and mitogen-stimulated cytokine profiles were measured in fasted blood samples, Epstein-Barr (EBV), varicella zoster (VZV), and herpes simplex 1 (HSV1) DNA was measured in saliva by quantitative polymerase chain reaction as an indicator of latent herpesvirus reactivation, and diet quality was determined using the healthy eating index measured by food frequency questionnaire in 61 US Army recruits (97% male) at the beginning (PRE) and end (POST) of 22-wk IMT. RESULTS: Lymphocytes and terminally differentiated cluster of differentiation (CD)4+ and CD8+ T cells increased PRE to POST, whereas granulocytes, monocytes, effector memory CD4+ and CD8+ T cells, and central memory CD8+ T cells decreased ( P ≤ 0.02). Cytokine responses to anti-CD3/CD28 stimulation were higher POST compared with PRE, whereas cytokine responses to lipopolysaccharide stimulation were generally blunted ( P < 0.05). Prevalence of EBV reactivation was higher at POST ( P = 0.04), but neither VZV nor HSV1 reactivation was observed. Diet quality improvements were correlated with CD8+ cell maturation and blunted proinflammatory cytokine responses to anti-CD3/CD28 stimulation. CONCLUSIONS: Lymphocytosis, maturation of T-cell subsets, and increased T-cell reactivity were evident POST compared with PRE IMT. Although EBV reactivation was more prevalent at POST, no evidence of VZV or HSV1 reactivation, which are more common during severe stress, was observed. Findings suggest increases in the incidence of EBV reactivation were likely appropriately controlled by recruits and immune-competence was not compromised at the end of IMT.


Assuntos
Militares , Esforço Físico , Privação do Sono , Estresse Psicológico , Feminino , Humanos , Masculino , Antígenos CD28/sangue , Linfócitos T CD8-Positivos/metabolismo , Citocinas/sangue , Estresse Psicológico/imunologia , Privação do Sono/imunologia , Linfócitos T CD4-Positivos/metabolismo , Esforço Físico/imunologia
18.
Asian J Psychiatr ; 79: 103400, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521406

RESUMO

BACKGROUND: Oxidative stress (OS) and neuroinflammatory pathways play an important role in the pathophysiology of schizophrenia. The present study investigated the relationship between OS, inflammatory cytokines, and clinical features in male patients with treatment-resistant schizophrenia (TRS). METHOD: We measured plasma OS parameters, including manganese-superoxide dismutase (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD), total-SOD (T-SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px); and serum inflammatory cytokines, including interleukin (IL)- 1α, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)-γ, from 80 male patients with chronic schizophrenia (31 had TRS and 49 had chronic stable schizophrenia (CSS)), and 42 healthy controls. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, plasma Mn-SOD, CuZn-SOD, T-SOD, GSH-Px, and MDA levels were significantly lower, while CAT and serum IL-6 levels were higher in both TRS and CSS male patients (all P < 0.05). Significant differences in the activities of CAT (F = 6.068, P = 0.016) and IL-6 levels (F = 6.876, P = 0.011) were observed between TRS and CSS male patients after analysis of covariance. Moreover, a significant positive correlation was found between IL-6 levels and PANSS general psychopathology subscores (r = 0.485, P = 0.006) and between CAT activity and PANSS total scores (r = 0.409, P = 0.022) in TRS male patients. CAT and IL-6 levels were predictors for TRS. Additionally, in chronic schizophrenia patients, a significant positive correlation was observed between IL-6 and GSH-Px (r = 0.292, P = 0.012), and the interaction effect of IL-6 and GSH-Px was positively associated with PANSS general psychopathology scores (r = 0.287, P = 0.014). CONCLUSION: This preliminary study indicated that variations in OS and inflammatory cytokines may be involved in psychopathology for patients with chronic schizophrenia, especially in male patients with TRS.


Assuntos
Catalase , Interleucina-6 , Esquizofrenia , Humanos , Masculino , Catalase/sangue , Catalase/química , Citocinas/sangue , Citocinas/química , Interleucina-6/sangue , Interleucina-6/química , Estresse Oxidativo/fisiologia , Esquizofrenia/diagnóstico , Esquizofrenia/metabolismo , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo
19.
Front Public Health ; 10: 1001340, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466533

RESUMO

Coronavirus disease 2019 (COVID-19) spread worldwide and presented a significant threat to people's health. Inappropriate disease assessment and treatment strategies bring a heavy burden on healthcare systems. Our study aimed to construct predictive models to assess patients with COVID-19 who may have poor prognoses early and accurately. This research performed a retrospective analysis on two cohorts of patients with COVID-19. Data from the Barcelona cohort were used as the training set, and data from the Rotterdam cohort were used as the validation set. Cox regression, logistic regression, and different machine learning methods including random forest (RF), support vector machine (SVM), and decision tree (DT) were performed to construct COVID-19 death prognostic models. Based on multiple clinical characteristics and blood inflammatory cytokines during the first day of hospitalization for the 138 patients with COVID-19, we constructed various models to predict the in-hospital mortality of patients with COVID-19. All the models showed outstanding performance in identifying high-risk patients with COVID-19. The accuracy of the logistic regression, RF, and DT models is 86.96, 80.43, and 85.51%, respectively. Advanced age and the abnormal expression of some inflammatory cytokines including IFN-α, IL-8, and IL-6 have been proven to be closely associated with the prognosis of patients with COVID-19. The models we developed can assist doctors in developing appropriate COVID-19 treatment strategies, including allocating limited medical resources more rationally and early intervention in high-risk groups.


Assuntos
COVID-19 , Citocinas , Aprendizado de Máquina , Humanos , COVID-19/mortalidade , Tratamento Farmacológico da COVID-19 , Citocinas/sangue , Citocinas/química , Hospitalização/estatística & dados numéricos , Estudos Retrospectivos
20.
Viruses ; 14(12)2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36560669

RESUMO

A better understanding of the immunological markers associated with long-lasting immune responses to SARS-CoV-2 infection is of paramount importance. In the present study, we characterized SARS-CoV-2-specific humoral responses in hospitalized (ICU and non-ICU) and non-hospitalized individuals at six months post-onset of symptoms (POS) (N = 95). We showed that the proportion of individuals with detectable anti-SARS-CoV-2 IgG or neutralizing (NAb) responses and the titers of antibodies were significantly reduced in non-hospitalized individuals, compared to ICU- or non-ICU-hospitalized individuals at 6 months POS. Interestingly, SARS-CoV-2-specific memory B cells persist at 6 months POS in both ICU and non-ICU patients and were enriched in cells harboring an activated and/or exhausted phenotype. The frequency/phenotype of SARS-CoV-2-specific memory B cells and the magnitude of IgG or NAb responses at 6 months POS correlated with the serum immune signature detected at patient admission. In particular, the serum levels of CXCL13, IL-1RA, and G-CSF directly correlated with the frequency of Spike-specific B cells and the magnitude of Spike-specific IgG or NAb, while the serum levels of CXCL12 showed an antagonizing effect. Our results indicate that the balance between CXCL12 and CXCL13 is an early marker associated with the magnitude and the quality of the SARS-CoV-2 humoral memory.


Assuntos
COVID-19 , Quimiocina CXCL12 , Quimiocina CXCL13 , Citocinas , Imunidade Humoral , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Quimiocina CXCL12/sangue , Quimiocina CXCL13/sangue , COVID-19/imunologia , Citocinas/sangue , Imunoglobulina G , SARS-CoV-2
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