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1.
Med Clin North Am ; 104(1): 1-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31757229

RESUMO

Physicians may encounter blood or tissue eosinophilia through a routine complete blood count with differential or a tissue pathology report. In this article, the basic biology of eosinophils is reviewed and definitions of blood eosinophilia, as well as the challenges of defining tissue eosinophilia, are discussed. Conditions associated with eosinophilia are briefly discussed as well as a general approach to evaluating eosinophilia. Future challenges include determining which eosinophil-associated diseases benefit from eosinophil-targeted therapy and identifying biomarkers for disease activity and diagnosis.


Assuntos
Eosinofilia/diagnóstico , Eosinófilos/metabolismo , Biomarcadores/sangue , Eosinofilia/sangue , Eosinofilia/etiologia , Humanos , Contagem de Leucócitos , Índice de Gravidade de Doença
2.
Int J Cancer ; 146(6): 1730-1740, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31840816

RESUMO

Immune checkpoint blockade (ICB) has shown long-term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment-induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti-CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti-CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti-CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Antígeno CTLA-4/antagonistas & inibidores , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Neoplasias/etiologia , Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Linhagem Celular Tumoral , Eosinófilos/imunologia , Feminino , Humanos , Imunidade , Imunomodulação/efeitos dos fármacos , Imunofenotipagem , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Depleção Linfocítica , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica/tratamento farmacológico , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
3.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(11): 850-856, 2019 Nov 07.
Artigo em Chinês | MEDLINE | ID: mdl-31795547

RESUMO

Objective: To explore the expression of amphiregulin (AREG) in nasal polyps patients with different degrees of eosinophil infiltration, and to analyze the correlation between AREG and tissue remodeling. Methods: Forty-eight patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery, Remin Hospital, Wuhan University from July 2017 to August 2018 were recruited, including 40 males and 8 females, aged from 16 to 60 years old. The subjects were divided into three groups: control group (n=14), eosinophilic chronic sinusitis with nasal polyps (ECRSwNP) group (n=19) and noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group (n=15). The relative expression of AREG in nasal mucosa was detected by Western blot assay and immunohistochemical staining. Tissue remodeling was detected by HE staining, AB-PAS staining and Masson staining. Kruskal-Wallis test was used for comparison among multiple groups, and Spearman correlation analysis was conducted between the expression level of AREG and the related indexes of tissue remodeling. Results: The expression of AREG in ECRSwNP group was significantly higher than that in non-ECRSwNP group and control group (median protein expression of Western blot was 1.592 vs 0.617 vs0.582, all P<0.05). The degree of epithelial injury and goblet cell metaplasia in ECRSwNP group was significantly higher than that in control group (all P<0.05), the percentage of collagen fibrosis area in ECRSwNP group was significantly lower than that in control group (P=0.01). In chronic rhinosinusitis with nasal polyps (CRSwNP) patients, the area of mucous glands was negatively correlated with the expression of AREG (r=-0.616, P<0.05), and the percentage of collagen fibrosis area was negatively correlated with the expression of AREG (r=-0.738, P<0.05). Conclusion: The expression of AREG is higher in ECRSwNP patients, which is related to the process of tissue remodeling.


Assuntos
Anfirregulina/biossíntese , Eosinófilos/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Doença Crônica , Feminino , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Rinite/patologia , Rinite/cirurgia , Sinusite/patologia , Sinusite/cirurgia , Adulto Jovem
4.
Expert Opin Drug Saf ; 18(12): 1161-1170, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31594389

RESUMO

Introduction: The last two decades have seen significant progress in the treatment of severe asthma especially the severe eosinophilic phenotype. This review article serves to update the reader on the known safety profiles of these medications. It does not serve as a review of their clinical efficacies.Areas covered: All four of the currently approved monoclonal antibodies (biologics) used in the treatment of severe asthma are discussed with reference to the known safety data garnered from clinical trials and real world evidence. A fifth, approved by The European Commission and FDA, but not yet by NICE or Health Canada, is also discussed.Expert opinion: For each of the five biologics the authors shall summarize the known safety profiles and also the potential adverse effects as their usage is extended long term with suggestions for real world studies to help us develop our knowledge base.


Assuntos
Antiasmáticos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Asma/tratamento farmacológico , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Asma/fisiopatologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Eosinófilos/metabolismo , Humanos , Índice de Gravidade de Doença
6.
Mol Immunol ; 114: 362-368, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31450181

RESUMO

Madi-Ryuk (MDR) is a traditional Korean medicine and it has been widely used in Korea to treat arthritis and we previously reported the anti-allergic inflammatory effect of MDR in vitro model. However, therapeutic evidence of MDR on in vivo model of allergic inflammatory reaction has not yet been demonstrated. The research purpose was to investigate the efficacy of MDR and its active ingredient tannic acid (TA) in ovalbumin (OVA)-induced AR mice model. OVA-challenged AR mice orally medicated MDR or its active ingredient TA daily for ten days. In mice having a AR, MDR and TA prominently diminished number of rubs and levels of histamine, IgE, thymic stromal lymphopoietin, interleukin (IL)-1ß, IL-4, IL-5, IL-13, IL-33, and tumor necrosis factor-α. In addition, protein expression levels and activities of caspase-1 were declined by oral medication of MDR and TA. Decline in levels of macrophage inflammatory protein-2 and intercellular adhesion molecules-1 and reduction in penetrations of inflammatory cells into inflamed tissue were also noted in MDR and TA groups. Taken together, identification of MDR effect in preclinical models suggests that MDR may be a therapeutic drug for the treatment and prevention of AR.


Assuntos
Anti-Inflamatórios/farmacologia , Rinite Alérgica/tratamento farmacológico , Taninos/farmacologia , Animais , Caspase 1/metabolismo , Quimiocina CXCL2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Histamina/metabolismo , Imunoglobulina E/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Medicina Tradicional Coreana/métodos , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Ovalbumina/farmacologia , Rinite Alérgica/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
Curr Med Sci ; 39(4): 560-567, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346991

RESUMO

Positive bronchodilation (BD) tests can be noticed in some stable chronic obstructive pulmonary disease (COPD) patients. The characteristics of airway inflammation in this entity remain unclear. Our study aimed to identify the characteristics of airway inflammation in stable COPD patients with positive BD tests. The airway inflammation was assessed in 88 patients with stable COPD using the examination of induced sputum in the aftermath of lung function and BD tests. Cellular counts and the levels of molecular markers including eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin-5 (IL-5), and IL-8 were assayed by Wright's stain, Immuno-CAP system, and ELISA, RT-PCR. Among the 88 patients with stable COPD, 20 (22.7%) showed positive BD tests. The values of eosinophils (4.7%±3.4%) and ECP (90.1±41.6 ng/mL) in induced sputum in stable COPD patients with positive BD tests were markedly elevated as compared with those in stable COPD patients with negative BD tests or in healthy controls (all P>0.05), but significantly lower than those in asthmatic patients (all P<0.01). The IL-5 in sputum supernatant was significantly decreased in stable COPD patients with positive BD tests as compared with the patients with asthma (12.5±7.8 vs. 48.2±26.0 ng/mL;.P<0.01). However, healthy controls exhibited similar concentrations of IL-5 in induced sputum with patients with stable COPD, whether with positive or negative BD tests (all P>0.05). Moreover, the values of neutrophils (61.8%±15.1%), MPO (574.0±111.8 ng/mL), and IL-8 (32.6±13.4 ng/mL) in induced sputum in stable COPD patients with positive BD tests were significantly higher than those in asthmatics or normal controls (all P<0.01). However, the values of the above inflammatory markers in induced sputum were similar among stable COPD patients with positive or negative BD tests (all P>0.05). The stable COPD patients with positive BD tests may present not only eosinophilic airway inflammation but also neutrophilic airway inflammation.


Assuntos
Asma/diagnóstico , Biomarcadores , Inflamação/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adolescente , Adulto , Idoso , Asma/genética , Asma/patologia , Broncodilatadores/administração & dosagem , Proteína Catiônica de Eosinófilo/genética , Eosinófilos/metabolismo , Eosinófilos/patologia , Feminino , Humanos , Inflamação/genética , Inflamação/patologia , Interleucina-5/genética , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Testes de Função Respiratória , Escarro/metabolismo , Adulto Jovem
9.
Immunol Allergy Clin North Am ; 39(3): 429-445, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31284931

RESUMO

Monoclonal antibodies block specific inflammatory pathways involved in the pathogenesis of asthma. These pathways are important in host defense against pathogens, and in particular, against parasites. Despite theoretical concerns about infection risk, biologics seem to have a favorable safety profile. Data from large clinical trials and postmarketing surveillance for these drugs have not shown increases in severe infections, including those from parasitic organisms. This may be due to redundancy of effector cells within the immune system. Certain drugs have special considerations and precautions, and therefore, the prescribing physician should be familiar with product recommendations and warnings.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , /etiologia , Animais , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Asma/complicações , Asma/diagnóstico , Asma/etiologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Eosinófilos/imunologia , Eosinófilos/metabolismo , Humanos , Imunoglobulina E/imunologia , Medição de Risco , Fatores de Risco , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
10.
Respir Res ; 20(1): 145, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291952

RESUMO

INTRODUCTION: Airway eosinophilic inflammation is a characteristic of asthmatic patients and of a sub group of COPD subjects. Blood eosinophils are deemed as a good surrogate marker of sputum eosinophilic inflammation; however, controversial data have been published particularly in COPD. The aim of our study was to compare blood and sputum eosinophils in COPD and asthmatic patients in "real life". METHODS: Sputum was induced in stable patients with COPD or asthma with hypertonic saline solution and blood eosinophils were evaluated. Frequency of comorbidities was recorded. Correlations were performed stratifying patients by disease and comorbidities. RESULTS: 146 patients, 57 with COPD and 89 with asthma were evaluated. Blood and sputum eosinophils expressed as percentages were correlated in COPD (rho = 0.40; p = 0.004), but the entity of correlation was lower compared with asthmatic subjects (rho = 0.71; p < 0.0001). When blood eosinophils were expressed as counts the correlation was slightly lower than when expressed as percentages in COPD (rho = 0.35; p = 0.01) and in asthmatic patients (rho = 0.68; p < 0.0001). In COPD patients older than 73 years or with blood eosinophils higher than the median value (210.6 eos/µl), or co-diagnosed with hypertension, ischemic heart disease or atrial fibrillation no correlation between blood and sputum eosinophils was found. However, the effect of ischemic heart disease and atrial fibrillation could be driven by hypertension since most of these patients have this comorbidity. CONCLUSION: Blood eosinophils correlated with sputum eosinophils to a lesser degree in COPD than in asthmatic patients. Older age, high blood eosinophils and hypertension affected the correlation between blood and sputum eosinophils, more studies are needed to evaluate the role of other cardiac comobidities.


Assuntos
Asma/sangue , Asma/diagnóstico , Eosinófilos/metabolismo , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Escarro/metabolismo , Idoso , Asma/imunologia , Eosinófilos/imunologia , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/imunologia , Escarro/imunologia
11.
Int J Chron Obstruct Pulmon Dis ; 14: 1045-1051, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190789

RESUMO

Many patients with chronic obstructive pulmonary disease (COPD) continue to experience exacerbations despite receiving standard-of-care treatments. Novel approaches to COPD treatment focus on understanding and targeting molecular mechanisms of airway inflammation, airway obstruction, remodeling and lung destruction. Several identified phenotypes and endotypes of COPD will pave the future path for a more personalized approach to therapy. Although well known to be associated with neutrophilic inflammation, COPD may also be driven by eosinophilic inflammation both at stable states and during exacerbation. Targeting eosinophilic inflammation has been successful in managing severe eosinophilic asthma and may hold promise in certain phenotypes of COPD. The most promising biologic treatments at an advanced stage of development are agents blocking interleukin (IL)-5 or its receptor. This review examines our current understanding of the eosinophilic inflammation in COPD and the rationale for IL-5 targeting agents.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Eosinófilos/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-5/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Eosinófilos/metabolismo , Interleucina-5/metabolismo , Subunidade alfa de Receptor de Interleucina-5/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Terapia de Alvo Molecular , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
12.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(6): 426-431, 2019 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-31189228

RESUMO

Objective: To compare the clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) by different levels of blood eosinophil (EOS) count and to investigate the predictive value of the response to glucocorticoid treatment and the readmission rate in the patients with higher blood eosinophils. Methods: A total of 120 patients with AECOPD were admitted to the Department of Pulmonary and Critical Care Medicine in The Second Xiangya Hospital of Central South University from January 01, 2017 to December 31, 2017. Patients were divided into two groups according to their admission blood eosinophil fractions. Patients with EOS%≥2% were in the EOS group (n=56) , while patients with EOS%<2% were in the Non-EOS group (n=64) . The clinical characteristics, hospitalization treatments especially the glucocorticoid treatment response were compared, and the risk of severe acute exacerbation of the two groups including the 12-month COPD-related readmission, and time to first COPD-related readmission were also compared. Results: Compared with the Non-EOS group, the EOS group had lower values of white blood cell (WBC) , neutrophil fraction (N%) , blood neutrophil-to-lymphocyte ratio (NLR) , and C-reactive protein (CRP) . The EOS group also required shorter course of antibiotic treatment [8 (6-10) and 9 (7-11) , P=0.033]. In glucocorticoid-treated patients (n=82) , the EOS group had significantly alleviated symptoms than the Non-EOS group (patients withδCAT≥2 were 86.8% and 68.2%, respectively, P=0.046) , and the duration of hospitalization of the EOS group was shorter [9 (7-11) and 10 (9 to 13) , P=0.042]. Patients with glucocorticoid treatment in the EOS group had significantly alleviated symptoms than those without glucocorticoid treatment (patients with δCAT ≥ 2 were 86.8% and 61.1%, respectively, P=0.040) . The follow-up one year after discharge showed a higher risk of severe acute exacerbation in the EOS group [Adjust OR 2.67 (1.10-6.46), P=0.030; HR: 1.57 (1.02-2.40), P=0.040]. Conclusion: The blood eosinophil levels were useful in predicting the AECOPD patients' response to glucocorticoid treatment and the risk of severe acute exacerbations.


Assuntos
Eosinofilia/complicações , Eosinófilos/metabolismo , Glucocorticoides/uso terapêutico , Readmissão do Paciente , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Biomarcadores/sangue , Progressão da Doença , Eosinofilia/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento
13.
J Immunol Res ; 2019: 9705327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214624

RESUMO

Galectin-1 (Gal-1) has immunomodulatory activities in various allergic inflammatory disorders, but its potential anti-inflammatory properties on allergic airway diseases have not been confirmed. We explored the pharmacological effects of Gal-1 on the progression of allergic airway inflammation and investigated the underlying mechanism. Female C57BL/6 mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-17 to establish an allergic airway inflammation model. In the challenge phase, a subset of mice was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). We found that rGal-1 inhibited pulmonary inflammatory cell recruitment, mucus secretion, bronchoalveolar lavage fluid (BALF) inflammatory cell infiltration, and cytokine production. The treatment also suppressed the infiltration of eosinophils into the allergic lung as indicated by decreased expression levels of eotaxin and eosinophil peroxidase (EPX). However, only the expression levels of IL-25, neither IL-33 nor TSLP, were significantly decreased in the lung by rGal-1 treatment. These immunomodulatory effects in the allergic lung were correlated with the activation of extracellular signal-regulated kinase (ERK) signaling pathway and downregulation of endogenous Gal-1. In addition, rGal-1 reduced the plasma concentrations of anti-OVA immunoglobulin E (IgE) and IL-17. Our findings suggest that rGal-1 is an effective therapy for allergic airway inflammation in a murine model and may be a potential pharmacological target for allergic airway inflammatory diseases.


Assuntos
Antineoplásicos/farmacologia , Hiper-Reatividade Brônquica/imunologia , Galectina 1/farmacologia , Alérgenos/imunologia , Animais , Hiper-Reatividade Brônquica/tratamento farmacológico , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/imunologia , Eosinófilos/metabolismo , Eosinófilos/patologia , Feminino , Expressão Gênica , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Sistema de Sinalização das MAP Quinases , Camundongos
14.
J Laryngol Otol ; 133(8): 678-684, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31218991

RESUMO

OBJECTIVE: This study aimed to determine the predictors of disease progression after functional endoscopic sinus surgery in patients with chronic rhinosinusitis. METHOD: A total of 281 adult chronic rhinosinusitis patients who underwent primary bilateral functional endoscopic sinus surgery between 2007 and 2017 and had at least 12 months of follow-up endoscopic evaluation were examined. Patients were divided into eosinophilic (n = 205) and non-eosinophilic chronic rhinosinusitis groups (n = 76). In order to determine adverse factors, post-operative endoscopic appearance scores were analysed in relation to the pre- and intra-operative findings using multiple regression analyses. RESULTS: The post-operative course of eosinophilic cases deteriorated over time, like the early period for non-eosinophilic cases. Frontal sinus polyps recurred early in eosinophilic chronic rhinosinusitis. Multivariate analyses indicated young adulthood, asthma, high computed tomography score and frontal sinus polyps as significant adverse predictors. CONCLUSION: Early, appropriate estimation of sinonasal conditions appears to be crucial for successful surgical management of chronic rhinosinusitis.


Assuntos
Eosinófilos/metabolismo , Seio Frontal/patologia , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Rinite/sangue , Rinite/diagnóstico , Fatores de Risco , Sinusite/sangue , Sinusite/diagnóstico , Adulto Jovem
15.
Food Chem Toxicol ; 131: 110577, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220534

RESUMO

Cadmium and aflatoxin B1 (AFB1) are both common and widespread pollutants in food and feed. There are several reports on toxicity induced by Cadmium or AFB1 alone, but few address the toxicity caused by co-exposure to the two substances. In this study, 42 female and 42 male Kunming (KM) mice were divided into seven groups to test the acute oral toxicity of CdCl2 and AFB1, using Karber's method. The combined toxicity was assessed using the Keplinger evaluation system. Acute toxicity symptoms, deaths, and body and organ weights were evaluated, and hematological, blood biochemical, and histopathological analyses were conducted. The results revealed the following median lethal doses (LD50): LD50(Female KM mice) = 62.56 mg/kg; LD50(Male KM mice) = 48.79 mg/kg; LD50(KM mice)=55.27 mg/kg. The combined toxicity of AFB1 and CdCl2 showed an additive effect in mice, and an increase in the mixed dose of AFB1 and CdCl2 resulted in greater toxicity. These results demonstrated that the combined toxicity of AFB1 and CdCl2 was greater than the toxicities of the individual components in mice; thus, this may cause particular challenges when addressing these hazards in food and feed and the associated risk to human and animal health.


Assuntos
Aflatoxina B1/toxicidade , Cádmio/toxicidade , Administração Oral , Aflatoxina B1/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Cádmio/administração & dosagem , Eosinófilos/metabolismo , Feminino , Rim/patologia , Contagem de Leucócitos , Fígado/patologia , Masculino , Camundongos , Neutrófilos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Testes de Toxicidade Aguda
16.
Int J Mol Sci ; 20(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216735

RESUMO

Bronchial asthma is a chronic disease characterized by reversible airway obstruction, mucus production, and bronchial hyperresponsiveness (BHR). Although Th2 cell-mediated eosinophilic inflammation is an important disease mechanism in the majority of patients with bronchial asthma, recent studies suggest the possible development of Th2-independent airway inflammation and BHR. These non-Th2 endotype patients seem to consist of multiple subgroups, and often do not respond to inhaled corticosteroids. Therefore, to understand the pathogenesis of asthma, it is important to characterize these non-Th2 subgroups. Recently, we demonstrated that Th9 cells induce eosinophil infiltration and eosinophil-independent BHR, and Th9 cells-mediated BHR may be resistant to glucocorticoid. In this review, we summarize the contribution of several T cell subsets in the development of bronchial asthma and introduce our recent study demonstrating Th9 cell-mediated and eosinophil-independent BHR.


Assuntos
Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/metabolismo , Eosinófilos/imunologia , Eosinófilos/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Hiper-Reatividade Brônquica/tratamento farmacológico , Humanos , Subpopulações de Linfócitos T/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo
17.
Respir Res ; 20(1): 83, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053134

RESUMO

BACKGROUND: An inverse relationship between oral corticosteroid (OCS) dose and peripheral blood eosinophil (PBE) count is widely recognized in patients with severe eosinophilic asthma; however, there are limited data available to quantify this relationship. This post hoc analysis of the SIRIUS study (NCT01691508) examined the impact of weekly incremental OCS dose reductions on PBE counts during the 3-8-week optimization phase of the study. METHODS: SIRIUS was a randomized, double-blind study involving patients with severe asthma (≥12 years old), which included an initial OCS dose optimization phase prior to randomization. Regression analysis assuming a linear relationship between change in OCS dose and change in log (PBE count) during the optimization phase was used to estimate the changes in PBE count following specific decreases in OCS dose. RESULTS: All 135 patients from the SIRIUS intent-to-treat population were included in this analysis. During the optimization period, 44% (60/135) of patients reduced their OCS dose, with an increase in geometric mean PBE count of 110 cells/µL (200 to 310 cells/µL; geometric mean ratio from beginning to end of the optimization phase: 1.52) recorded in these patients. The model estimated that reduction of daily OCS dose by 5 mg/day led to a 41% increase in PBE count (mean ratio to beginning of optimization phase: 1.41 [95% confidence interval (CI); 1.22, 1.63]). CONCLUSION: These data confirmed and quantified the inverse association between OCS dose and PBE count. These insights will help to inform clinicians when tapering OCS doses in patients with severe eosinophilic asthma.


Assuntos
Corticosteroides/administração & dosagem , Asma/sangue , Asma/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Índice de Gravidade de Doença , Administração Oral , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino
18.
Mol Cells ; 42(4): 345-355, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31082802

RESUMO

Eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most challenging problems in clinical rhinology. FZD5 is a receptor for Wnt5A, and its complex with Wnt5A contributes to activating inflammation and tissue modification. Nasal polyps and eosinophil/non-eosinophil counts are reported to be directly correlated. This study investigated the expression and distribution of FZD5, and the role of eosinophil infiltration and FZD5 in eosinophilic CRSwNP pathogenesis. The prognostic role of eosinophil levels was evaluated in seven patients with CRSwNP. Fifteen patients with CRS were classified based on the percentage of eosinophils in nasal polyp tissue. Methylated genes were detected using methyl-CpG-binding domain sequencing, and qRT-PCR and immunohistochemistry were used to detect FZD5 expression in nasal polyp tissue samples. The results showed that mRNA expression of FZD5 was upregulated in nasal polyps. FZD5 expression was significantly higher in nasal polyp samples from patients with eosinophilic CRSwNP than in those from patients with non-eosinophilic CRSwNP, as indicated by immunohistochemistry. Furthermore, inflammatory cytokine levels were higher in eosinophilic CRSwNP-derived epithelial cells than in normal tissues. In conclusion, FZD5 expression in nasal mucosal epithelial cells is correlated with inflammatory cells and might play a role in the pathogenesis of eosinophilic CRSwNP.


Assuntos
Metilação de DNA , Eosinófilos/metabolismo , Receptores Frizzled/genética , Pólipos Nasais/genética , Rinite/genética , Sinusite/genética , Adulto , Idoso , Citocinas/metabolismo , Epigênese Genética , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Receptores Frizzled/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/citologia , Mucosa Nasal/metabolismo , Pólipos Nasais/imunologia , Prognóstico , Regiões Promotoras Genéticas , Rinite/imunologia , Sinusite/imunologia , Regulação para Cima
20.
N Engl J Med ; 381(11): 1023-1034, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31112385

RESUMO

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known. METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo. CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Eosinófilos/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Receptores de Interleucina-5/antagonistas & inibidores , Idoso , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Doença Pulmonar Obstrutiva Crônica/imunologia
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