RESUMO
Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Hepatite C/tratamento farmacológico , Adulto , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/fisiopatologia , Egito/epidemiologia , Feminino , Hepacivirus/metabolismo , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/virologia , Humanos , Interleucina-13/análise , Interleucina-13/sangue , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatologia , Masculino , MicroRNAs/análise , MicroRNAs/sangue , MicroRNAs/uso terapêutico , Pessoa de Meia-Idade , Falha de Tratamento , Carga Viral/métodos , Vitamina D/análise , Vitamina D/sangueRESUMO
Group 2 innate lymphoid cells (ILC2s) are early effectors of mucosal type 2 immunity, producing cytokines such as interleukin (IL)-13 to mediate responses to helminth infection and allergen-induced inflammation. ILC2s are also present in lymph nodes (LNs) and can express molecules required for antigen presentation, but to date there are limited data on their dynamic behaviour. We used a CD2/IL-13 dual fluorescent reporter mouse for in vivo imaging of ILC2s and Th2 T cells in real time following a type 2 priming helminth infection or egg injection. After helminth challenge, we found that ILC2s were the main source of IL-13 in lymphoid organs (Peyer's patches and peripheral LNs), and were located in T cell areas. Intravital imaging demonstrated an increase in IL-13+ ILC2 size and movement following helminth infection, but reduced duration of interactions with T cells compared with those in homeostasis. In contrast, in the intestinal mucosa, we observed an increase in ILC2-T cell interactions post-infection, including some of prolonged duration, as well as increased IL-13+ ILC2 movement. These data suggest that ILC2 activation enhances cell motility, with the potential to increase the area of distribution of cytokines to optimise the early generation of type 2 responses. The prolonged ILC2 interactions with T cells within the intestinal mucosa are consistent with the conclusion that contact-based T cell activation may occur within inflamed tissues rather than lymphoid organs. Our findings have important implications for our understanding of the in vivo biology of ILC2s and the way in which these cells facilitate adaptive immune responses.
Assuntos
Enteropatias Parasitárias/imunologia , Subpopulações de Linfócitos/imunologia , Nippostrongylus , Esquistossomose mansoni/imunologia , Infecções por Strongylida/imunologia , Células Th2/imunologia , Animais , Genes Reporter , Interleucina-13/análise , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Intestino Delgado/parasitologia , Microscopia Intravital , Contagem de Linfócitos , Subpopulações de Linfócitos/química , Camundongos , Especificidade de Órgãos , Organismos Livres de Patógenos Específicos , Células Th2/químicaRESUMO
The occurrence of asthma is closely related to environmental factors such as cigarette smoke (CS), one of the common risk factors. Environmental stimuli have the potential to activate transient receptor potential ankyrin 1 (TRPA1) and cause or aggravate asthma. The destruction of tight junctions (TJs) between airway epithelial cells by environmental stimuli in asthma has been researched. It is worth exploring whether CS can injury TJs and aggravate asthma by activating TRPA1. The objective of this study was to investigate the aggravation of CS on ovalbumin (OVA)-induced asthma related phenotypes and TJs expression in mice, and to explore the relationship between TRPA1 and the expression of TJs protein. Female wild type (WT) C57BL/6 mice, induced by OVA, CS and OVA plus CS (OVA + CS) respectively, were used to establish a 42-day asthma model, and mice with TRPA1 knockout (TRPA1-/-) were treated in the same way. This study detected the number of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF), the levels of IL-4, IL-5, IL-13 in BALF, enhanced pause (Penh) of lung function, pathological changes and the gene and protein expressions of TRPA1 and TJs (including ZO-1, Occludin and Claudin-2) in lung tissues. Compared with normal saline (NS) group, WT mice in the OVA group and OVA + CS group were significantly higher in asthma related phenotypes. The WT-OVA + CS group also showed higher Penh value, levels of IL-5 and IL-13 in BALF and lung tissue injury scores when compared with the WT-OVA group and WT-CS group. However, WT-OVA + CS group mice had significantly larger number of neutrophils in BALF than the WT-OVA group, and had larger number of eosinophils in peripheral blood and higher levels of IL-4 in BALF than the WT-CS group. Meanwhile, compared with the WT-NS group, the expressions of TRPA1 and Claudin-2 in lung tissues increased in other three groups while their expressions of ZO-1 and Occludin decreased, among which, the WT-OVA + CS group showed more remarkable changes. Compared with the WT-OVA + CS group, mice in the TRPA1-/--OVA + CS showed a significant decrease in the number of inflammatory cells, levels of IL-4, IL-5 and IL-13 in BALF, Penh value and lung tissue injury score, and a downregulation of Claudin-2 expression while an upregulation of ZO-1 and Occludin expressions. In addition, the airway inflammation and injury, and the expressions of ZO-1, Occluding and Claudin-2 expressions were found with no statistic differences between TRPA1-/--OVA group and TRPA1-/--OVA + CS group. These results suggest that CS has aggravated the airway inflammation, pathological damage and destruction of TJs in airway epithelium of OVA-induced asthmatic mice, the processes of which are related to the increase of TRPA1 expression.
Assuntos
Asma/patologia , Fumaça/efeitos adversos , Fumar/efeitos adversos , Canal de Cátion TRPA1/metabolismo , Junções Íntimas/patologia , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Claudinas/metabolismo , Modelos Animais de Doenças , Ativação Enzimática , Interleucina-13/análise , Interleucina-4/análise , Interleucina-5/análise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ocludina/metabolismo , Ovalbumina/toxicidade , Canal de Cátion TRPA1/genética , Nicotiana/toxicidade , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
BACKGROUND: Persistent allergic airway diseases cause a great burden worldwide. Their pathogenesis is not clear enough. There is evidence that one of the recently described cytokine interleukin (IL) 22 may be involved in the pathogenesis of these diseases. Scientists argue if this cytokine acts as proinflammatory or anti-inflammatory agent. The aim of this study was to investigate IL-22 level in patients with persistent allergic airway diseases caused by house dust mite (HDM) in comparison with healthy individuals and to evaluate its relationship with IL-13 and IL-10 level, symptoms score and quality of life. METHODS: Patients with persistent allergic rhinitis caused by HDM and having symptoms for at least 2 years with or without allergic asthma were involved into the study. Measurements of IL-22, IL-13 and IL-10 and in serum and nasal lavage was performed by ELISA. Questionnaires assessing symptoms severity and quality of life were used. RESULTS: A tendency was observed that IL-22 in serum and nasal lavage was higher in patients with allergic airway diseases compared to control group (14.86 pg/ml vs. 7.04 pg/ml and 2.67 pg/ml vs. 1.28 pg/ml, respectively). Positive statistically significant correlation was estimated between serum IL-22 and serum IL-10 (rs = 0.57, p < 0.01) and IL-13 (rs = 0.44, p < 0.05) level. Moreover, positive significant correlation was found between IL-22 in nasal lavage and IL-10 in nasal lavage (rs = 0.37, p < 0.05). There was a negative statistically significant correlation between serum IL-22 and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) (rs = - 0.42, p < 0.05). CONCLUSION: Our study showed a possible anti-inflammatory effect of IL-22 in patients with persistent allergic airway diseases caused by HDM.
Assuntos
Asma/complicações , Interleucinas/análise , Líquido da Lavagem Nasal/química , Pyroglyphidae/imunologia , Rinite Alérgica/imunologia , Adulto , Animais , Anti-Inflamatórios , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-10/análise , Interleucina-13/análise , Masculino , Projetos Piloto , Rinite Alérgica/sangue , Inquéritos e Questionários , Interleucina 22RESUMO
OBJECTIVE: To analyze the effect of statins on cytokines levels in gingival crevicular fluid (GCF) and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). METHODS: Systemically healthy controls (C group, n = 62), T2DM patients not taking statins (D group, n = 57) and T2DM patients taking statins (S group, n = 24) were recruited. In each group, subjects (40-85 years) were subclassified into the h (periodontal health)group, the g (gingivitis)group or the p (periodontitis) group according to different periodontal conditions. 17 cytokines in gingival crevicular fluid (GCF) and saliva samples of each subject were measured utilizing the Luminex technology kit. Further, HbA1c (glycated hemoglobin), FPG (fasting plasma glucose), PD (probing depth), CAL (clinical attachment level), BOP (bleeding on probing), GI (gingival index) and PI (periodontal index) were recorded. Data distribution was tested through the Shapiro-Wilk test, upon which the Kruskal-Wallis test was applied followed by Mann-Whitney U test and Bonferroni's correction. RESULTS: Levels of IFN-γ, IL-5, IL-10 and IL-13 in the saliva of the Dh group were significantly lower than those in the Ch group, while factor IL-4 was higher (p<0.05). Levels of MIP-3α, IL-7 and IL-2 in GCF of the Dh group were considerably higher than those in the Ch group (p<0.05), while that of IL-23 was considerably lower. Compared with the Cg group, levels of IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-13 were significantly lower in the saliva of the Dg group (p<0.05). Lower levels of IFN-γ, IL-5 and IL-10 were detected in the Sg group than those in the Cg group (p<0.05). At the same time, levels of IL-1ß, IL-6, IL-7, IL-13, IL-17, IL-21 and MIP-3α in the gingival crevicular fluid of the Sg group were lower in comparison with the Dg group. In addition, lower levels of IL-4 and higher levels of IL-7 in GCF were identified in the Dg group than those in the Cg group, while in the Sg group, lower levels of IL-4, MIP-1αand MIP-3αwere observed than those in the Cg group (p<0.05). Lower levels of IFN-γ, IL-6, IL-10, IL-13 and I-TAC were found in the Sp group compared with those in the Cp group. The IFN-γ, IL-6 and IL-10 levels were lower in the Dp group than those in the Cp group (p<0.05). Meanwhile, in the Sp group, lower levels of pro-inflammatory factors IFN-γ, IL-1ß, IL-2, IL-6, IL-7, IL-21 and TNF-α, in addition to higher levels of anti-inflammatory factors IL-4 and IL-5 in gingival crevicular fluid, were identified than those in the Dp group. Higher levels of IFN-γ,IL-1ß,IL-2,IL-7,IL-21 and TNF-α and a lower level of IL-5 in the Dp group were identified than those in the Cp group (p<0.05). Moreover, statins were able to substantially reduce PD in T2DM patients with periodontitis, indicating an obvious influence on the levels of cytokines secreted by Th1 cells, Th2 cells and Th17 cells, as revealed by PCA (principal component analysis). CONCLUSION: Statins are associated with reduced PD and cytokines levels in the GCF and saliva of T2DM patients with periodontitis.
Assuntos
Citocinas/análise , Diabetes Mellitus Tipo 2/patologia , Líquido do Sulco Gengival/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Saliva/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Gengivite/patologia , Humanos , Interferon gama/análise , Interleucina-10/análise , Interleucina-13/análise , Masculino , Pessoa de Meia-Idade , Periodontite/complicações , Periodontite/patologia , Análise de Componente PrincipalAssuntos
Dermatite Atópica/diagnóstico , Interleucina-13/análise , Subunidade alfa de Receptor de Interleucina-4/análise , Pele/patologia , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/metabolismo , Biópsia , Estudos de Casos e Controles , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Feminino , Voluntários Saudáveis , Humanos , Imuno-Histoquímica , Interleucina-13/metabolismo , Subunidade alfa de Receptor de Interleucina-4/metabolismo , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Masculino , Melanócitos/imunologia , Melanócitos/metabolismo , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele/citologia , Pele/imunologia , Adulto JovemRESUMO
Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffused inflammation of the colon and rectum mucosa. The pathogenesis of UC is multifactorial, and the exact underlying mechanisms remain poorly understood. This study aims to investigate the effect of mesalazine and atorvastatin combination in enhancing anti-inflammatory effects and attenuates progression of oxazolone colitis in rats. In the present study, male albino rats (N = 60) were divided into six groups (10 rats each), the first two groups served as normal control and a control saline group. Colitis was induced by intra-rectal administration of oxazolone in the 5th and 7th days after pre-sensitization. Then, rats were divided into untreated group, groups treated with mesalazine or atorvastatin or their combination. Colitis was assessed by colon length, body weight, and incidence of diarrhea, rectal bleeding, and histopathology of colon tissue. Colon tissues were used for measuring interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-13, signal transducer and activator of transcription-3 (STAT-3), myeloperoxidase activity (MPO), reduced glutathione(GSH), and tissue expression of IL-10, tight junction protein zonula occludens (ZO-1), and caspase-3 genes. The combination therapy significantly attenuated progression of UC by decreasing incidence of diarrhea, rectal bleeding, weight loss, IL-13, IL-6, TNF-α, STAT-3, caspase-3, and MPO activity and significantly increased IL-10, ZO-1, colon length, and GSH content, and these effects were more superior to single drugs. These findings showed that combination therapy was able to ameliorate progression of UC and enhance anti-inflammatory effects possibly by restoring IL-10 and ZO-1 levels and limiting IL-6/STAT-3 trans-signaling.
Assuntos
Anti-Inflamatórios/farmacologia , Atorvastatina/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Interleucina-10/genética , Mesalamina/administração & dosagem , Proteína da Zônula de Oclusão-1/genética , Animais , Atorvastatina/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Colo/metabolismo , Colo/patologia , Quimioterapia Combinada , Interleucina-13/análise , Interleucina-6/fisiologia , Masculino , Mesalamina/farmacologia , Oxazolona/toxicidade , Ratos , Fator de Transcrição STAT3/fisiologia , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: This study aimed to explore the prognostic value of particulate matter with a diameter of ≤2.5 µm (PM2.5)-related microRNA-206 combined with interleukin (IL)-4, IL-13 and interferon-γ (INF-γ) in asthma induced pulmonary arterial hypertension (PAH). METHODS: Fifty SPF BALB/c mice were divided into 5 groups: control group, asthma + PAH group, low-toxic asthma + PAH group, moderately-exposed asthma + PAH group, highly-exposed asthma + PAH group. Differences of microRNA-206, IL-4, IL-13, and INF-γ expression in lung tissue and plasma were detected. A total of 98 patients with asthma induced PAH and 98 healthy persons were collected. Patients were followed up for 12 months. RESULTS: Based on microarray analyses, we found that microRNA-206 may be involved in asthma induced PAH stimulated by PM2.5. Compared with healthy people, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in asthma induced PAH patients were significantly higher (P< .05). Compared with survivors, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in non-survivors were significantly higher (P< .05). Survival analyses showed that compared with low microRNA-206, low IL-4, low IL-13 and low INF-γ groups, survival rate of patients in high microRNA-206 (χ2 = 4.864, P= .013), high IL-4 (χ2 = 3.774, P= .038), high IL-13 (χ2 = 8.375, P< .001) and high INF-γ groups (χ2 = 9.007, P< .001) were significantly reduced. Established prognostic evaluation model was built and the estimated probability was 0.473. Compared with estimated probability ≤ 0.473, survival rate of patients in estimated probability> 0.473 was significantly reduced (χ2 = 17.377, P< .001). CONCLUSION: Current model combining plasma microRNA-206, IL-4, IL-13, and INF-γ has potential significance for prognosis of asthma induced PAH.
Assuntos
Asma , Interferon gama , Interleucina-13 , Interleucina-4 , Pulmão/metabolismo , MicroRNAs , Material Particulado , Hipertensão Arterial Pulmonar , Animais , Asma/complicações , Asma/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Interferon gama/análise , Interferon gama/sangue , Interleucina-13/análise , Interleucina-13/sangue , Interleucina-4/análise , Interleucina-4/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/análise , MicroRNAs/sangue , Pessoa de Meia-Idade , Material Particulado/efeitos adversos , Material Particulado/análise , Prognóstico , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/metabolismoRESUMO
INTRODUCTION: Asthma diagnosis in young children may represent a clinical challenge. There are no standard prognostic and dia-gnostic methods. The aim of the study was to evaluate the clinical and prognostic assessment of IL-4 and IL-13 concentrations in children with recurrent wheezing. MATERIAL AND METHODS: The study included 96 children with recurrent wheezing. 81 patients were diagnosed as transient wheezing, 15 patients with asthma, and 25 healthy children were selected as controls. The concentrations of IL-4 and IL-13 were analyzed in exhaled breath condensate (EBC) using an enzyme-linked immunosorbent assay (ELISA). Data analysis was performed using Statsoft Statistica Version 8 (Tulsa, OK) and the statistical program MedCalc version 17.2. RESULTS: Both IL-4 and IL-13 concentrations were significantly higher in DDA (21.13 pg/mL, 26.13 pg/mL, respectively) and TW (13.86 pg/mL, 18.3 pg/mL, respectively) groups as compared to healthy controls (3.37 pg/mL, 16.35 pg/mL, respectively; p<0.001), and the highest rates were observed in children with diagnosed asthma (p < 0.001, DDW vs TW, respectively). IL-4 concentration higher than 18.45 pg/mL (with sensitivity 86.7% and specificity 80%) and IL-13 concentration higher than 20.17pg/ /mL (with sensitivity 100% and specificity 76.7%) in EBC in children with wheezing recurrence can be considered as a possible predictor of asthma development. CONCLUSIONS: The concentration of the anti-inflammatory cytokines IL-4 and IL-13 were significantly increased in children with recurrent wheezing and the highest rates were found in asthma developing children. The concentrations of IL-4 and IL-13 in chil-dren with wheezing can be considered as a possible predictor of asthma development.
Assuntos
Asma/imunologia , Asma/metabolismo , Interleucina-13/análise , Interleucina-4/análise , Biomarcadores/análise , Testes Respiratórios/métodos , Estudos de Casos e Controles , Criança , Feminino , Humanos , MasculinoRESUMO
Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.
Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Citocinas/análise , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Análise por Conglomerados , Citocinas/imunologia , Eosinófilos/imunologia , Feminino , Humanos , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Interleucina-13/análise , Interleucina-13/imunologia , Interleucina-5/análise , Interleucina-5/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Linfócitos T/citologia , Linfócitos T/imunologia , Carga Viral , Adulto JovemRESUMO
Characteristic of allergic asthma, CD4+Th2 lymphocytes secrete Th2 cytokines, interleukin (IL)-4, IL-13, and IL-5 that mediate the inflammatory immune response. Surface expression of CD2 and its ligand, CD58, is increased on the monocytes and eosinophils of asthma patients, which correlate with elevated serum IgE levels, suggesting that CD2 may contribute to allergic airway inflammation. Using a murine model of asthma, we observed that house dust mice extract (HDME)-exposed Balb/c mice have increased airway hyperresponsiveness (AHR), lung inflammation, goblet cell hyperplasia, and elevated levels of Th2 cytokines in the lungs, as well as increased serum IgE levels as compared to the control mice. In contrast, with the exception of serum IgE levels, all the other parameters were significantly reduced in HDME-treated Cd2-/- mice. Interestingly, Il13 but not Il4 or Il5 gene expression in the lungs was dramatically decreased in HDME-exposed Cd2-/- mice. Of note, the gene expression of IL-13 downstream targets (Muc5b and Muc5ac) and high affinity IL-13Rα2 were upregulated in the lungs of HDME-exposed Balb/c mice but were significantly reduced in HDME-exposed Cd2-/- mice. Consistently, gene expression of microRNAs regulating mucin production, inflammation, airway smooth muscle cell proliferation and IL-13 transcripts were increased in the lungs of HDME-exposed Cd2-/- mice. Given the established role of IL-13 in promoting goblet cell hyperplasia, lung inflammation and AHR in allergic asthma, our studies reveal a unique role for CD2 in the regulation of Th2-associated allergic asthma.
Assuntos
Asma/genética , Asma/fisiopatologia , Antígenos CD2/genética , Pulmão/imunologia , Pyroglyphidae/química , Pyroglyphidae/imunologia , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/análise , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Inflamação/etiologia , Interleucina-13/análise , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hipersensibilidade Respiratória/etiologia , Células Th2/imunologiaRESUMO
BACKGROUND: One of the hallmarks of bullous pemphigoid (BP) is moderate to severe chronic itch. Managing this is difficult because little is known about the mechanisms of itch in BP. OBJECTIVE: We sought to elucidate the pathophysiologic mechanisms of itch in BP. METHODS: The expression of itch mediators in lesions of 24 patients with BP and 6 healthy individuals were examined through immunofluorescence staining. Furthermore, the expression of itch mediators and itch severity was correlated. RESULTS: Itch severity was correlated with eosinophils, substance P, neurokinin 1R, interleukin (IL) 31 receptor A, oncostatin M receptor-ß, IL-13, periostin, and basophils. There was also a trend between itch severity and IL-31 expression. Most of the cells expressing IL-31 or neurokinin 1R were identified as eosinophils. Intraepidermal nerve fiber density was decreased. Other itch mediators, including mast cells, IL-4, thymic stromal lymphopoietin, transient receptor potential vanilloid 1 and ankyrin 1, and protease activated receptor 2 were not significantly correlated with itch severity. LIMITATIONS: The relatively small sample size, the examination of protein expression exclusively through immunofluorescent analysis, and lack of functional assays in patients are the limitations. CONCLUSIONS: Multiple factors are involved in BP-associated itch, including eosinophils, substance P, neurokinin 1R, IL-31, IL-31 receptor A, oncostatin M receptor-ß, IL-13, periostin, and basophils. They could be useful therapeutic targets.
Assuntos
Penfigoide Bolhoso/fisiopatologia , Prurido/etiologia , Pele/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Basófilos/fisiologia , Moléculas de Adesão Celular/análise , Doença Crônica , Citocinas/imunologia , Eosinófilos/fisiologia , Feminino , Imunofluorescência , Humanos , Interleucina-13/análise , Masculino , Pessoa de Meia-Idade , Subunidade beta de Receptor de Oncostatina M/análise , Penfigoide Bolhoso/imunologia , Receptores de Interleucina/análise , Receptores da Neurocinina-1/análise , Índice de Gravidade de Doença , Pele/química , Pele/imunologia , Substância P/análise , Células Th2/imunologiaRESUMO
Background: Increasing evidence from rodent studies indicates that inhaled multi-walled carbon nanotubes (MWCNTs) have harmful effects on the lungs. In this study, we examined the effects of inhalation exposure to MWCNTs on allergen-induced airway inflammation and fibrosis. We hypothesized that inhalation pre-exposure to MWCNTs would render mice susceptible to developing allergic lung disease induced by house dust mite (HDM) allergen. Methods: Male B6C3F1/N mice were exposed by whole-body inhalation for 6 h a day, 5 d a week, for 30 d to air control or 0.06, 0.2, and 0.6 mg/m3 of MWCNTs. The exposure atmospheres were agglomerates (1.4-1.8 µm) composed of MWCNTs (average diameter 16 nm; average length 2.4 µm; 0.52% Ni). Mice then received 25 µg of HDM extract by intranasal instillation 6 times over 3 weeks. Necropsy was performed at 3 and 30 d after the final HDM dose to collect serum, bronchoalveolar lavage fluid (BALF), and lung tissue for histopathology. Results: MWCNT exposure at the highest dose inhibited HDM-induced serum IgE levels, IL-13 protein levels in BALF, and airway mucus production. However, perivascular and peribronchiolar inflammatory lesions were observed in the lungs of mice at 3 d with MWCNT and HDM, but not MWCNT or HDM alone. Moreover, combined HDM and MWCNT exposure increased airway fibrosis in the lungs of mice. Conclusions: Inhalation pre-exposure to MWCNTs inhibited HDM-induced TH2 immune responses, yet this combined exposure resulted in vascular inflammation and airway fibrosis, indicating that MWCNT pre-exposure alters the immune response to allergens.
Assuntos
Antígenos de Dermatophagoides/imunologia , Hipersensibilidade/fisiopatologia , Exposição por Inalação/efeitos adversos , Pulmão/fisiologia , Nanotubos de Carbono/toxicidade , Animais , Líquido da Lavagem Broncoalveolar , Relação Dose-Resposta Imunológica , Fibrose , Imunoglobulina E/sangue , Interleucina-13/análise , Masculino , Camundongos , Células Th2/imunologiaRESUMO
BACKGROUND: Intraluminal contributor(s) to airflow obstruction in severe asthma are patient-specific and must be evaluated to personalize treatment. The occurrence and functional consequence of airway mucus in the presence or absence of airway eosinophils remain undetermined. OBJECTIVE: The objective of this study was to understand the functional consequence of airway mucus in the presence or absence of eosinophils and to identify biomarkers of mucus-related airflow obstruction. METHODS: Mucus plugs were quantified on CT scans, and their contribution to ventilation heterogeneity (using MRI ventilation defect percent [VDP]) was evaluated in 27 patients with severe asthma. Patients were dichotomized based on sputum eosinophilia such that the relationship between mucus, eosinophilia, and ventilation heterogeneity could be investigated. Fractional exhaled nitric oxide (Feno) and related cytokines in sputum were measured. RESULTS: Mucus plugging was present in 100% of asthma patients with sputum eosinophils and 36% of those without sputum eosinophils (P = .0006) and was correlated with MRI VDP prebronchodilator (r = 0.68; P = .0001) and postbronchodilator (r = 0.72; P < .0001). In a multivariable regression, both mucus and eosinophils contributed to the prediction of postbronchodilator MRI VDP (R2 = 0.75; P < .0001). Patients with asthma in whom the mucus score was high had raised Feno (P = .03) and IL-4 (P = .02) values. Mucus plugging correlated with Feno (r = 0.63; P = .005). CONCLUSIONS: Both airway eosinophils and mucus can contribute to ventilation heterogeneity in patients with severe asthma. Patients in whom mucus is the dominant cause of airway obstruction have evidence of an upregulated IL-4/IL-13 pathway that could be identified according to increased Feno level.
Assuntos
Asma , Biomarcadores/análise , Eosinófilos/patologia , Imageamento por Ressonância Magnética/métodos , Muco , Tomografia Computadorizada por Raios X/métodos , Manuseio das Vias Aéreas/métodos , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/imunologia , Obstrução das Vias Respiratórias/patologia , Asma/sangue , Asma/diagnóstico , Asma/fisiopatologia , Correlação de Dados , Feminino , Humanos , Interleucina-13/análise , Interleucina-4/análise , Contagem de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Depuração Mucociliar , Muco/citologia , Muco/diagnóstico por imagem , Óxido Nítrico/análise , Ventilação Pulmonar , Índice de Gravidade de Doença , Escarro/citologia , Escarro/diagnóstico por imagemRESUMO
BACKGROUND & OBJECTIVES: Atopic dermatitis (AD) is one of the most common pathologic conditions of skin in children. The effect of breastfeeding on the risk of AD remains controversial. The aim of this study was to determine the counts of cytokine-producing cells in the mothers' breast milk of infants with and without AD to assess association, if any. METHODS: Breast milk samples (10 ml) were obtained from mothers of 25 infants with AD and of 26 healthy infants as a control group. The number of cytokine-producing cells including interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin-13 (IL-13) and IL-4 in the milk samples was determined using an enzyme-linked immunospot assay technique. RESULTS: The mean of IL-13-producing cells in milk was significantly lower in mothers of AD-affected infants in comparison with mothers of normal infants (324.91±255.45 vs. 538.93±465.39, P<0.05). There were no significant differences between mothers of infants with and without AD regarding milk count of IFN-γ-, TNF-α- and IL-4-producing cells. INTERPRETATION & CONCLUSIONS: Our results showed lower number of IL-13-producing cells in milk of mothers of infants with AD. Therefore, lower count of IL-13-producing cells in mothers' milk may confer a susceptibility to AD. Further studies with a large number of samples need to be done to confirm our findings.
Assuntos
Aleitamento Materno , Interleucina-13/análise , Contagem de Linfócitos/métodos , Leite Humano/imunologia , Linfócitos T , Correlação de Dados , Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Feminino , Humanos , Lactente , Interferon gama/análise , Interleucina-4/análise , Masculino , Linfócitos T/imunologia , Linfócitos T/fisiologia , Fator de Necrose Tumoral alfa/análiseRESUMO
OBJECTIVE: To investigate the correlations of inflammatory factors, interleukin-6 (IL-6), IL-10, IL-13 and tumor necrosis factor-α (TNF-α), and composition of bacterial flora in the peritoneal fluid with infertility in endometriosis patients. PATIENTS AND METHODS: A total of 55 patients diagnosed with endometriosis and infertility in the Gynecology Clinic of our hospital from June 2014 to July 2017 were selected as observation group, and another 30 non-endometriosis and non-infertility patients were enrolled as control group. The peritoneal fluid was extracted from patients in both groups, and the total white cell count and the percentage of leukocyte subset were determined. The total genome deoxyribonucleic acid (DNA) of microorganisms in peritoneal fluid was extracted, and the composition of microorganisms was analyzed using the Ion Torrent PGM platform (BGI). The levels of IL-6, IL-10, IL-13, and TNF-α in peritoneal fluid were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the correlations of inflammatory factors in the peritoneal fluid with endometriosis complicated with infertility were analyzed via Logistic regression analysis. RESULTS: The total white cell count, monocytes, neutrophils, eosinophils and basophils in endometriosis patients complicated with infertility were significantly higher than those in control group (p<0.05). Results of ELISA showed that the levels of IL-6, IL-10, IL-13, and TNF-α in peritoneal fluid of endometriosis patients complicated with infertility were significantly higher than those in control group (p<0.05). In peritoneal fluid of patients in both groups, Proteobacteria and Firmicutes were mainly dominated, followed by Actinobacillus, Bacteroidetes, Fusobacteria and Tenericutes, and there was no significant difference in the Eumycota between the two groups (p>0.05). Logistic regression analysis results showed that there were significant correlations of inflammatory factors (IL-6, IL-10, IL-13, and TNF-α) with endometriosis complicated with infertility. CONCLUSIONS: There are many kinds of Eumycota in the peritoneal fluid of endometriosis patients complicated with infertility, but they are not the main pathogenic factors. Inflammatory factors (IL-6, IL-10, IL-13, and TNF-α) can be used as important reference indexes for the diagnosis of endometriosis complicated with infertility.
Assuntos
Líquido Ascítico/química , Líquido Ascítico/microbiologia , Endometriose/metabolismo , Endometriose/microbiologia , Infertilidade Feminina/metabolismo , Infertilidade Feminina/microbiologia , Mediadores da Inflamação/análise , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Endometriose/complicações , Endometriose/fisiopatologia , Feminino , Fertilidade , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Interleucina-10/análise , Interleucina-13/análise , Interleucina-6/análise , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/análise , Regulação para CimaRESUMO
BACKGROUND: Sinonasal disease is a common feature of cystic fibrosis (CF) and can cause significant morbidity in these patients. Our objective was to determine if CF individuals with concomitant nasal polyposis (NP) express a unique profile of inflammation and if so, whether these inflammatory cytokine mediators have predictive value in identifying these individuals for prompt management by an Otolaryngologist. METHODOLOGY: Nasal lavage samples and clinical outcomes of disease severity were obtained from thirty-eight pediatric CF individuals. Participants were subdivided based on the presence or absence of NP. Nasal lavage samples were analyzed on a panel of seventeen cytokine targets using a Bio-Plex Luminex assay. A Perl Permutation test with correction for multiple hypotheses was performed to identify uniquely expressed cytokines between CF individuals with NP (CFwNP) and those without (CFsNP). RESULTS: Thirty-five patients were included in the analysis. Cytokines IL-13 and GM-CSF were uniquely expressed in the CFwNP group when compared to the CFsNP group. Logistic regression analysis demonstrated a significant association of IL-13 with NP. CONCLUSION: In children diagnosed with CF, the level of IL-13 in nasal lavage samples could potentially serve as a non-invasive clinical tool in predicting NP in this population, and a target for future immunotherapy.
Assuntos
Fibrose Cística/complicações , Interleucina-13/análise , Pólipos Nasais/etiologia , Criança , Estudos Transversais , Citocinas/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Masculino , Lavagem Nasal , Valor Preditivo dos TestesRESUMO
Schistosomiasis is a chronic helminthic disease causing hepatic fibrosis. Some studies demonstrated direct effect of targeting apoptosis on fibrosis regression. This study is a novel trial of Paeoniflorin (PAE) on S. mansoni induced hepatic fibrosis in murine model compared to Praziquantel (PZQ) evaluating their anti-parasitic and anti-fibrotic properties aiming to discover a new therapy that decrease schistosomiasis morbidity. Thirty two laboratory bred Swiss albino male CD-1 mice were used in this study. The mice were classified into four groups (8 mice each), control healthy, control infected, PZQ treated (300 mg/kg/12 h), PAE treated (50 mg/kg/d) groups. All mice groups were sacrificed 15 weeks post infection for assessment of drugs efficacy by parasitological, histopathological, immunohistochemical and serological studies. Our results showed that PAE improved the parasitological parameters including decrease worm burden, immature, mature eggs and increase dead ones yet, still PZQ had the upper hand in this aspect. However, PAE exceeded PZQ as an anti-fibrotic therapy seemed in marked decrease in hepatic mean granuloma diameter and fibrosis area, besides, marked increase in serum tumor necrosis factor-alpha; TNF-α level, caspase-3 and P53 apoptotic expressions. There was marked decrease in serum IL-13 level, nuclear factor-kappa B; NF-kB, Transforming Growth Factor-Beta1; TGF-ß1, Alpha-Smooth Muscle Actin; α-SMA fibrotic expressions. Conclusively, PAE could be an anti schistosomiasis mansoni therapy exceeding PZQ in targeting apoptosis and ameliorating fibrosis. This study provides a perspective for a novel therapeutic approach to prevent liver fibrosis following liver injury due to schistosomiasis mansoni.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Glucosídeos/farmacologia , Cirrose Hepática/tratamento farmacológico , Monoterpenos/farmacologia , Esquistossomose mansoni/tratamento farmacológico , Actinas/análise , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomphalaria , Feminino , Glucosídeos/uso terapêutico , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Interleucina-13/análise , Fígado/química , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/etiologia , Masculino , Camundongos , Monoterpenos/uso terapêutico , NF-kappa B/análise , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Esquistossomose mansoni/complicações , Esquistossomose mansoni/patologia , Fator de Crescimento Transformador beta1/análise , Fator de Necrose Tumoral alfa/análiseRESUMO
PURPOSE: Diabetic patients seem to be predisposed to cutaneous candidiasis. In this study, we evaluated the interference of diabetic conditions in alloxan-induced diabetic mice in relation to the development of C. albicans infection, density of M1 and M2 macrophages, distribution of collagen type I and III and anti-inflamamatory cytokines involved in tissue repair. METHODOLOGY: The mice were treated with intravenous alloxan, and all animals with blood glucose levels >250 mg dl-1 were inoculate with C. albicans intradermally in the hind paw and were studied for up to 21 days. Control groups without alloxan were used. The fungal burden was evaluated by periodic acid-Schiff (PAS) and by counting the colony forming units. Total population of macrophages were targeted with antibody to F4/80 antigen and M2 macrophages with anti-arginase antibody. Anti-inflammatory cytokines from popliteal lymph nodes were determined by capture ELISA procedures. Picrosirius red staining allowed qunantification of collagen types I and III in the infected skin by using a polarized light microscope.Results/Key findings. Diabetic mice, versus non-diabetic mice, showed a significant lower density of F4/80 and M2 macrophages, higher fungal burden, deficiency in interleukin (IL)-4 production, and delayed IL-13 responses. The later clearance of C. albicans enhanced tissue injury, leading to a decrease in collagen type I. Moreover, collagen type III was increased by interference of IL-13 and transforming growth factor-ß cytokines. CONCLUSION: These findings highlight some important changes in diabetic animal responses to C. albicans infection that may be important to the pathophysiological processes underpinning cutaneous candidiasis in diabetic patients.
Assuntos
Candidíase Cutânea/microbiologia , Candidíase Cutânea/fisiopatologia , Diabetes Mellitus Experimental/complicações , Cicatrização , Animais , Glicemia/análise , Candida albicans/crescimento & desenvolvimento , Candida albicans/imunologia , Candida albicans/fisiologia , Candidíase Cutânea/etiologia , Candidíase Cutânea/imunologia , Colágeno/análise , Citocinas/análise , Citocinas/imunologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/fisiopatologia , Modelos Animais de Doenças , Interleucina-13/análise , Interleucina-4/análise , Macrófagos/imunologia , Masculino , Camundongos , Pele/químicaRESUMO
The role of breastfeeding in improving allergy outcomes in early childhood is still unclear. Evidence suggests that immune mediators in human milk (HM) play a critical role in infant immune maturation as well as protection against atopy/allergy development. We investigated relationships between levels of immune mediators in colostrum and mature milk and infant outcomes in the first year of life. In a large prospective study of 398 pregnant/lactating women in the United Kingdom, Russia and Italy, colostrum and mature human milk (HM) samples were analysed for immune active molecules. Statistical analyses used models adjusting for the site of collection, colostrum collection time, parity and maternal atopic status. Preliminary univariate analysis showed detectable interleukin (IL) 2 and IL13 in HM to be associated with less eczema. This finding was further confirmed in multivariate analysis, with detectable HM IL13 showing protective effect OR 0.18 (95% CI 0.04-0.92). In contrast, a higher risk of eczema was associated with higher HM concentrations of transforming growth factor ß (TGFß) 2 OR 1.04 (95% CI 1.01-1.06) per ng/mL. Parental-reported food allergy was reported less often when IL13 was detectable in colostrum OR 0.10 (95% CI 0.01-0.83). HM hepatocyte growth factor (HGF) was protective for common cold incidence at 12 months OR 0.19 (95% CI 0.04-0.92) per ng/mL. Data from this study suggests that differences in the individual immune composition of HM may have an influence on early life infant health outcomes. Increased TGFß2 levels in HM are associated with a higher incidence of reported eczema, with detectable IL13 in colostrum showing protective effects for food allergy and sensitization. HGF shows some protective effect on common cold incidence at one year of age. Future studies should be focused on maternal genotype, human milk microbiome and diet influence on human milk immune composition and both short- and long-term health outcomes in the infant.