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Parasite Immunol ; 40(10): e12579, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30107039


Chronic helminth infection with Schistosoma (S.) mansoni protects against allergic airway inflammation (AAI) in mice and is associated with reduced Th2 responses to inhaled allergens in humans, despite the presence of schistosome-specific Th2 immunity. Schistosome eggs strongly induce type 2 immunity and allow to study the dynamics of Th2 versus regulatory responses in the absence of worms. Treatment with isolated S. mansoni eggs by i.p. injection prior to induction of AAI to ovalbumin (OVA)/alum led to significantly reduced AAI as assessed by less BAL and lung eosinophilia, less cellular influx into lung tissue, less OVA-specific Th2 cytokines in lungs and lung-draining mediastinal lymph nodes and less circulating allergen-specific IgG1 and IgE antibodies. While OVA-specific Th2 responses were inhibited, treatment induced a strong systemic Th2 response to the eggs. The protective effect of S. mansoni eggs was unaltered in µMT mice lacking mature (B2) B cells and unaffected by Treg cell depletion using anti-CD25 blocking antibodies during egg treatment and allergic sensitization. Notably, prophylactic egg treatment resulted in a reduced influx of pro-inflammatory, monocyte-derived dendritic cells into lung tissue of allergic mice following challenge. Altogether, S. mansoni eggs can protect against the development of AAI, despite strong egg-specific Th2 responses.

Anticorpos Antiprotozoários/sangue , Asma/prevenção & controle , Óvulo/imunologia , Schistosoma mansoni/imunologia , Alérgenos/imunologia , Compostos de Alúmen/farmacologia , Animais , Anticorpos Antiprotozoários/imunologia , Asma/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Eosinofilia/prevenção & controle , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Inflamação/patologia , Subunidade alfa de Receptor de Interleucina-2 , Pulmão/imunologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Ovalbumina/farmacologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia
Clin Immunol ; 188: 1-6, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29183867


Mucus hypersecretion and eosinophil infiltration are important characteristics of eosinophilic inflammation in upper airways, such as allergic rhinitis and chronic rhinosinusitis with nasal polyp. EGFR transactivation induces mucus and inflammatory cytokine secretion from airway epithelial cells. However, the roles of EGFR in eosinophilic inflammation in upper airways are still unknown. The purpose of the study is to elucidate the effects of the EGFR inhibitor AG1478 on eosinophilic airway inflammation. AG1478 significantly inhibited thrombin-induced GM-CSF secretion from nasal epithelial cells and thrombin-induced secretion of eotaxin-1 and RANTES from nasal fibroblasts. Intranasal instillation of AG1478 inhibited OVA-induced goblet cell metaplasia, mucus production and eosinophil/neutrophil infiltration in rat nasal epithelium, as did intraperitoneal injection of AG1478. These results indicate that EGFR transactivation plays an important role in eosinophilic airway inflammation. Intranasal instillation of an EGFR inhibitor may be a new therapeutic approach for the treatment of intractable eosinophilic inflammation in upper airways.

Eosinófilos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Inflamação/prevenção & controle , Quinazolinas/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Tirfostinas/farmacologia , Administração Intranasal , Animais , Células Cultivadas , Quimiocina CCL11/metabolismo , Quimiocina CCL5/metabolismo , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Eosinofilia/metabolismo , Eosinofilia/prevenção & controle , Eosinófilos/metabolismo , Eosinófilos/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Receptores ErbB/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Inflamação/metabolismo , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Infiltração de Neutrófilos/efeitos dos fármacos , Quinazolinas/administração & dosagem , Ratos , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Trombina/farmacologia , Tirfostinas/administração & dosagem
J Ethnopharmacol ; 216: 251-258, 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29247697


ETHNOPHARMACOLOGICAL RELEVANCE: Seed kernel of the plant Ceasalpinia bonducella Linn (Caesalpiniacaeae) are used for the treatment of asthma in folk medicine and ancient books. AIM OF STUDY: To assess the pharmacological efficacy of the plant in asthma and to confine and describe the synthetic constituents from the seeds that are in charge of the action. MATERIAL AND METHODS: The viability of petroleum ether, ethanol extract and ethyl acetate fraction from ethanol extract of C. bonducella seeds were screened for the treatment of asthma by various methods viz. effect of test drug on clonidine and haloperidol induced catalepsy, milk-induced leukocytosis and eosinophilia, mast cell stabilizing activity in mice and studies on smooth muscle preparation of guinea pig ileum (in-vitro). Column chromatography of active extract was done to pinpoint the active compound followed by structure elucidation by FTIR, GCMS and NMR spectroscopic methods. RESULTS: Ethyl acetate fraction from ethanol extract of C. bonducella seeds exhibited antihistaminic activity at the dose of 50 and 100 mg/kg, inhibited clonidine-induced catalepsy but not haloperidol-induced catalepsy. Ethyl acetate fraction from ethanol extract significantly inhibited increased leukocyte and eosinophil count due to milk allergen and showed maximum protection against mast cell degranulation by clonidine. The results of guinea pig ileum indicated that the compound 2 methyl, 1 hexadecanol isolated from ethyl acetate fraction of ethanol extract relaxed significantly the ileum muscle strips pre-contracted by which suggests the involvement of ß2-agonists on the relaxation of the tissue. All the results are dose dependent. Active ethyl acetate fraction from ethanol extract showed presence of anti-asthmatic compound, 2-methyl, 1-hexadecanol. CONCLUSION: The ethyl acetate fraction from ethanol extract of seeds of the plant C. bonducella can inhibit parameters linked to asthma disease.

Antialérgicos/farmacologia , Antiasmáticos/farmacologia , Caesalpinia , Antagonistas dos Receptores Histamínicos/farmacologia , Extratos Vegetais/farmacologia , Sementes , Acetatos/química , Animais , Antialérgicos/isolamento & purificação , Antialérgicos/toxicidade , Antiasmáticos/isolamento & purificação , Antiasmáticos/toxicidade , Caesalpinia/química , Caesalpinia/toxicidade , Catalepsia/induzido quimicamente , Catalepsia/prevenção & controle , Degranulação Celular/efeitos dos fármacos , Clonidina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eosinofilia/induzido quimicamente , Eosinofilia/prevenção & controle , Feminino , Cobaias , Haloperidol , Antagonistas dos Receptores Histamínicos/isolamento & purificação , Antagonistas dos Receptores Histamínicos/toxicidade , Íleo/efeitos dos fármacos , Íleo/metabolismo , Dose Letal Mediana , Leucocitose/induzido quimicamente , Leucocitose/prevenção & controle , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Leite , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Receptores Adrenérgicos beta 2/metabolismo , Sementes/química , Sementes/toxicidade , Solventes/química , Fatores de Tempo
Allergy ; 73(2): 369-378, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28857178


BACKGROUND: Asthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega-6 fatty acid, is metabolized into cysteinyl leukotriene with pro-inflammatory properties for allergic inflammation, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti-inflammatory effects. In this study, we investigated the mechanism underlying the counter-regulatory roles of EPA in inflamed lungs. METHODS: Male C57BL6 mice were sensitized and challenged by ovalbumin (OVA). After EPA treatment, we evaluated the cell count of Bronchoalveolar lavage fluid (BALF), mRNA expressions in the lungs by q-PCR, and the amounts of lipid mediators by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics. We investigated the effect of the metabolite of EPA by in vivo and in vitro studies. RESULTS: Eicosapentaenoic acid treatment reduced the accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA-derived metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12-OH-17,18-EpETE attenuated airway eosinophilic inflammation through downregulation of C-C chemokine motif 11 (CCL11) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin-4. CONCLUSION: These results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12-OH-17,18-EpETE is a potential therapeutic target for the management of asthma.

Anti-Inflamatórios/farmacologia , Ácidos Araquidônicos/farmacologia , Asma/prevenção & controle , Eosinofilia/prevenção & controle , Inflamação/fisiopatologia , Pulmão/fisiopatologia , Animais , Asma/imunologia , Asma/fisiopatologia , Modelos Animais de Doenças , Eosinofilia/imunologia , Eosinofilia/fisiopatologia , Inflamação/imunologia , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 35(10): 617-623, dic. 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-169560


Algunas enfermedades infecciosas han adquirido más relevancia por el aumento de los movimientos poblacionales. La eosinofilia es un hallazgo frecuente en inmigrantes y en viajeros. Una de las causas más frecuentes de eosinofilia es la infección por helmintos y algunos protozoos intestinales. El objetivo de este trabajo es describir las características epidemiológicas de los casos con eosinofilia y su asociación con la presencia de parásitos en la red de datos REDIVI. Se trata de un estudio observacional multicéntrico prospectivo, donde se incluyen los casos diagnosticados de eosinofilia registrados en la Red cooperativa para el estudio de las infecciones importadas por viajeros e inmigrantes (+REDIVI) desde enero de 2009 hasta diciembre de 2012. Se registraron en la red un total de 5.255 episodios durante el periodo de estudio, y la eosinofilia fue un hallazgo en el 8,1 al 31,3% de los casos (dependiendo del tipo migratorio). Fueron hombres el 60,2%, con una mediana de 31,0años, inmigrantes el 72,4% y asintomáticos el 81,2%. Los parásitos más frecuentemente identificados fueron S.stercoralis(34,4%), Schistosoma sp. (11,0%) y uncinarias (8,6%). Existía asociación entre eosinofilia y presencia de parásitos para todos los helmintos (excepto para larva migrans cutánea). La sintomatología y la duración del viaje no determinaron significativamente la presencia de eosinofilia. Ante una eosinofilia en una persona que ha vivido en zonas endémicas de helmintiasis es aconsejable realizar estudios dirigidos para su diagnóstico, independientemente del tipo migratorio, la duración de la estancia o la presencia de sintomatología (AU)

The population movements during the last decades have resulted in a progressively increasing interest in certain infectious diseases. Eosinophilia is a common finding in immigrants and travelers. One of the most common causes of eosinophilia is helminth infection, and some intestinal protozoa. The aim of this paper is to describe the epidemiological characteristics of cases with eosinophilia and its association with the presence of parasites in the REDIVI data network. This is a multicenter prospective observational study that includes patients diagnosed with eosinophilia registered in the cooperative network for the study of infectious diseases in travelers and immigrants (+REDIVI) from January 2009 to December 2012. A total of 5,255 episodes were recorded in the network during the study period, and eosinophilia was observed in 8.1-31.3% of cases (depending on the immigration group). There were 60.2% men, with a median age of 31years. There were 72.4% immigrants, and 81.2% were asymptomatic. The most commonly identified parasites were S.stercoralis (34.4%), Schistosoma sp. (11.0%), and hookworm (8.6%). The relationship between eosinophilia and parasite infection was significant for all helminths (except for cutaneous larva migrans). The symptoms and duration of the journey did not significantly determine the presence of eosinophilia. In the case of eosinophilia in a person who has lived in helminth endemic areas, it is advisable to carry out targeted studies to diagnose the infection, regardless of immigration type, length of stay, or the presence of symptoms (AU)

Humanos , Eosinofilia/epidemiologia , Eosinofilia/prevenção & controle , Saúde do Viajante , Fatores de Risco , Emigrantes e Imigrantes , Protocolos Clínicos , Doenças Transmissíveis/epidemiologia , Estudos Prospectivos , Eosinofilia/microbiologia , Medicina de Viagem/normas , Eosinofilia/parasitologia
Rhinology ; 55(2): 152-160, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28501884


BACKGROUND: Periostin is a recently discovered biomarker for eosinophilic inflammation. Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed chronic inflammatory airway disease. Medical treatments aim to relieve symptoms and maintain clinical control by interfering with the inflammatory cascade. The effect on nasal and serum periostin levels is however yet unknown. We aimed to evaluate the effect of omalizumab, mepolizumab, methylprednisolone and doxycycline on nasal and systemic periostin expression. METHODS: This study is based on 3 previously published trials. Nasal and systemic periostin were assessed in CRSwNP patients, randomly assigned to receive doxycycline (n=14), methylprednisolone (n=14), mepolizumab (n=20) or omalizumab (n=15). There was a control group for each treatment scheme. Doxycycline (200 mg on the first day, followed by 100 mg once daily) and methylprednisolone (32-8 mg once daily) were administered during 20 days; mepolizumab was injected at baseline and at 4 weeks. Omalizumab was injected every 2 or 4 weeks, following the official drug leaflet. RESULTS: Methylprednisolone and omalizumab significantly reduced serum periostin levels at 4 and 8 weeks, respectively, after the start of the treatment. The effect of methylprednisolone was transient. Nasal periostin levels decreased significantly after 8 weeks of treatment with mepolizumab. The periostin expression is in accordance with the previously reported effect on the eosinophilic inflammation and clinical outcome. CONCLUSION: All treatment options distinctly influence periostin expression, reflecting the interference with the local or systemic eosinophilic inflammatory cascade.

Moléculas de Adesão Celular/metabolismo , Pólipos Nasais/complicações , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Administração Oral , Antialérgicos/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/análise , Doença Crônica , Doxiciclina/uso terapêutico , Eosinofilia/prevenção & controle , Feminino , Humanos , Inflamação/prevenção & controle , Injeções , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Omalizumab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite/etiologia , Sinusite/etiologia , Resultado do Tratamento
Ann Hematol ; 96(7): 1211-1213, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28432410

Fatores Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma de Efusão Primária/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Idoso de 80 Anos ou mais , DNA Viral/sangue , Erupção por Droga/etiologia , Erupção por Droga/prevenção & controle , Monitoramento de Medicamentos , Eosinofilia/induzido quimicamente , Eosinofilia/prevenção & controle , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/imunologia , Tumores do Estroma Gastrointestinal/patologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/metabolismo , Humanos , Fatores Imunológicos/efeitos adversos , Lenalidomida/efeitos adversos , Linfoma de Efusão Primária/diagnóstico por imagem , Linfoma de Efusão Primária/imunologia , Linfoma de Efusão Primária/virologia , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Segunda Neoplasia Primária/diagnóstico por imagem , Segunda Neoplasia Primária/imunologia , Segunda Neoplasia Primária/virologia , Radiografia Torácica , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
Ren Fail ; 38(1): 65-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26554528


Hemodialysis-associated eosinophilia (HAE) is believed to be associated with allergic reactions to dialyzer materials. This study aimed to investigate the use of Polyflux membranes to improve HAE. Thirty-one patients suffering from HAE were included. Patients were dialyzed with polysulfone membranes when they developed HAE. After that, patients were dialyzed with Polyflux membranes three times every week, 4 h every time without changing the dialysis parameters and medication. Levels of peripheral eosinophils, hsCRP, IgE, C3a, IL-5 and peripheral CD4+ lymphocytes and CD8+ lymphocytes were assessed before Polyflux treatment, and at 4th, 8th and 12th weeks of treatment. Any symptoms including chest tightness and skin itching were observed during the study period. After 12 weeks of Polyflux membrane dialysis and compared with polysulfone membrane dialysis, levels of peripheral eosinophils were significantly decreased (1.26 ± 0.61 vs. 0.71 ± 0.29 × 10(9)/L, p < 0.001); serum IL-5 levels were significantly decreased (24.43 ± 10.21 vs. 9.11 ± 4.21 pg/mL, p < 0.001); and chest tightness and skin itching were significantly improved (45.2% vs. 19.4%, p = 0.028). After 12 weeks, there was no significant change in serum levels of hsCRP (2.00 ± 0.94 vs. 1.81 ± 0.79 mg/L, p = 0.352), IgE (104.61 ± 98.79 vs. 114.95 ± 101.07 IU/mL, p = 0.422) and C3a (121.61 ± 34.04 vs. 120.29 ± 32.81 µg/L, p = 0.316), and in peripheral levels of CD4+ (589 ± 181 vs. 569 ± 171 cells/mm(3), p = 0.672) and CD8+ (443 ± 123 vs. 414 ± 140 cells/mm(3), p = 0.395) cells. Eosinophil count was correlated with serum IL-5 levels (r = 0.873, p < 0.001). Changing to a Polyflux membrane may alleviate HAE and reduce serum IL-5 levels. Therefore, this could be a strategy to manage HAE in the clinical practice.

Eosinofilia/prevenção & controle , Membranas Artificiais , Diálise Renal/efeitos adversos , Idoso , Proteína C-Reativa/metabolismo , Complemento C3a/metabolismo , Eosinofilia/sangue , Eosinofilia/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Interleucina-5/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Diálise Renal/instrumentação
Arterioscler Thromb Vasc Biol ; 35(12): 2526-35, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26494229


OBJECTIVE: Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. APPROACH AND RESULTS: We demonstrate that CD25(+) ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr(-/-)rag1(-/-) mice. To investigate the role of ILCs in atherosclerosis, ldlr(-/-)rag1(-/-) mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or IL-2/anti-IL-2 complexes that expand CD25(+) ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti-IL-2-treated mice. These IL-2-treated mice had reduced very low-density lipoprotein cholesterol and increased triglycerides compared with controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila, and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2 complex-induced eosinophilia but did not change lesion size. CONCLUSIONS: This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in very low-density lipoprotein cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis.

Anticorpos/farmacologia , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-2/farmacologia , Linfócitos/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/imunologia , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/imunologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Apolipoproteínas B/sangue , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/sangue , VLDL-Colesterol/sangue , Modelos Animais de Doenças , Eosinofilia/imunologia , Eosinofilia/metabolismo , Eosinofilia/prevenção & controle , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-5/antagonistas & inibidores , Interleucina-5/sangue , Interleucina-5/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de LDL/deficiência , Receptores de LDL/genética , Triglicerídeos/sangue
Immunol Lett ; 163(2): 173-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25530546


Puerarin is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been used as a prescribed drug in China for the treatment of many diseases in the clinical practice. The present study aimed to determine the protective effects and the underlying mechanisms of puerarin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and puerarin (10 mg/kg, 20 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Th1/Th2 cytokines were measured by enzyme-linked immunosorbent assay, eotaxin-3 was evaluated by western blotting. Our study demonstrated that, compared with model group, puerarin inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4, IL-5, IL-13 levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that puerarin substantially inhibited OVA-induced eosinophilia in lung tissue compared with model group. Western blotting studies demonstrated that puerarin substantially inhibited eotaxin-3 compared with model group. Our findings support puerarin can prevent some signs of allergic asthma in the mouse model.

Asma/prevenção & controle , Quimiocinas CC/antagonistas & inibidores , Inflamação/prevenção & controle , Isoflavonas/farmacologia , Sistema Respiratório/efeitos dos fármacos , Animais , Asma/induzido quimicamente , Asma/metabolismo , Western Blotting , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Quimiocina CCL26 , Quimiocinas CC/metabolismo , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Eosinofilia/induzido quimicamente , Eosinofilia/metabolismo , Eosinofilia/prevenção & controle , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Fitoterapia/métodos , Pueraria/química , Distribuição Aleatória , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , Células Th1/metabolismo , Células Th2/metabolismo
Acta Trop ; 141(Pt A): 46-53, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25312338


Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis.

Angiostrongylus cantonensis/fisiologia , Encefalomielite/epidemiologia , Eosinofilia/epidemiologia , Encefalite Infecciosa/epidemiologia , Estágios do Ciclo de Vida , Meningite/epidemiologia , Infecções por Strongylida/epidemiologia , Animais , Ásia/epidemiologia , Encefalomielite/prevenção & controle , Encefalomielite/terapia , Eosinofilia/prevenção & controle , Eosinofilia/terapia , Humanos , Encefalite Infecciosa/prevenção & controle , Encefalite Infecciosa/terapia , Larva/fisiologia , Meningite/prevenção & controle , Meningite/terapia , Infecções por Strongylida/prevenção & controle , Infecções por Strongylida/terapia
J. investig. allergol. clin. immunol ; 25(1): 1-11, 2015. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-134342


Allergic diseases are characterized by tissue eosinophilia, mucus secretion, IgE production, and activation of mast cells and TH2 cells. Production of TH2 cytokines including IL-4, IL-5, IL-9, and IL-13 has mainly been attributed to CD4+ T 2 cells. However, the recent discovery of group 2 innate lymphoid cells (ILC2s) in humans and findings from experimental disease models have challenged conventional concepts associated with the contribution of specific cells to type 2 inflammation in allergic diseases. ILC2s produce high levels of T H 2 cytokines and have been detected in human lung tissue, peripheral blood, the gastrointestinal tract, skin, and sinonasal tissue, suggesting that ILC2s could contribute to chronic rhinosinusitis, asthma, atopic dermatitis, and gastrointestinal allergic disease. Moreover, depletion of ILC2s in animal models suggests a role for these cells in atopic dermatitis and asthma. This review will focus on the role of ILC2s in human allergy and asthma and provide a mechanistic insight from animal models (AU)

Las enfermedades alérgicas se caracterizan por una eosinifilia tisular, producción de moco, producción de IgE, y por activación de mastocitos y células Th2. A estas células se ha atribuido la producción predominante de citocinas IL-4, IL-5, IL-9 y IL-13. Sin embargo el descubrimiento reciente en humanos de las células linfoides innatas grupo 2 y los hallazgos en modelos experimentales de enfermedad han cuestionado nuestros conceptos convencionales sobre las células que contribuyen a la inflamación tipo 2 presente en las enfermedades alérgicas. Las células ILC2 producen grandes cantidades de citocinas Th2 y se han podido detectar en el pulmón humano, en sangre periférica, tracto gastrointestinal, piel y tejido rinosinusal. Este hecho sugiere que estas células ILC2 podrían contribuir a la fisiopatología de la rinosinusitis, asma, dermatitis atópica y enfermedad gastrointestinal. Además la deplección de estas células en modelos animales sugiere su papel en la dermatitis atópica y en el asma. Esta revisión trata sobre el papel de las células ILC2 en alergia y asma humana, y ofrece una visión mecanística basada en resultados obtenidos en modelos animales (AU)

Animais , Linfócitos/citologia , Linfócitos/patologia , Hipersensibilidade/diagnóstico , Eosinofilia/sangue , Eosinofilia/fisiopatologia , Citocinas/administração & dosagem , Trato Gastrointestinal/lesões , Dermatite Atópica/enzimologia , Rinite Alérgica Perene/metabolismo , Linfócitos/metabolismo , Hipersensibilidade/patologia , Eosinofilia/diagnóstico , Eosinofilia/prevenção & controle , Trato Gastrointestinal/anormalidades , Dermatite Atópica/patologia , Rinite Alérgica Perene/diagnóstico
Immunobiology ; 219(7): 565-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24731407


Astragaloside IV is the chief ingredient of Radix Astragali, which has been used in the Traditional Chinese Medicine as a major component of many polyherbal formulations for the repair and regeneration of injured organ and tissues. We tested the anti-asthmatic effects of AST IV and the possible mechanisms. BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with AST IV (40mg/kg and 20mg/kg) 1h before they were challenged with OVA. Our study demonstrated that AST IV inhibited OVA-induced increases in eosinophil count; interleukin (IL)-4 level were recovered in bronchoalveolar lavage fluid increased IFN-γ and IL-10 levels in bronchoalveolar lavage fluid. Histological studies demonstrated that AST IV substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that AST IV substantially increased CD4(+)CD25(+)Foxp3 T cells (Treg). Furthermore quantitative real-time (qPCR) studies demonstrated that AST IV substantially enhanced Foxp3 mRNA expression in lung tissue. These findings suggest that AST IV may effectively ameliorate the progression of airway inflammation and could be used as a therapy for patients with allergic inflammation.

Asma/imunologia , Citocinas/imunologia , Inflamação/imunologia , Saponinas/imunologia , Linfócitos T Reguladores/imunologia , Triterpenos/imunologia , Animais , Antiasmáticos/imunologia , Antiasmáticos/farmacologia , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/farmacologia , Asma/induzido quimicamente , Asma/prevenção & controle , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/prevenção & controle , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Eosinofilia/induzido quimicamente , Eosinofilia/imunologia , Eosinofilia/prevenção & controle , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Inflamação/prevenção & controle , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-10/imunologia , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Saponinas/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Triterpenos/farmacologia
Rev. esp. investig. oftalmol ; 3(4): 227-229, oct.-dic. 2013. ilus
Artigo em Espanhol | IBECS | ID: ibc-132296


Caso Clínico: varón de 24 años procedente de Guinea Ecuatorial que durante su ingreso por una tuberculosis pulmonar resistente al tratamiento refiere molestias oculares. Las analíticas de control revelaron una gran eosinofilia. Fue remitido a consulta al referir gran sensación de cuerpo extraño en el ojo izquierdo sobre todo por las noches. A la exploración evidenciamos hiperemia conjuntival y epiescleral y la presencia de un gusano adulto a nivel subconjuntival que fue retirado en quirófano. Ante la gran sospecha de loiasis se toman muestras de hemocultivo confirmando la presencia de microfilarias. Tras la recuperación de la enfermedad pulmonar se procede al tratamiento sistémico contra el Loa-loa. Discusión: debemos resaltar que la loiasis ocular es una parasitosis bastante frecuente en las zonas endémicas del centro de África, sin embargo en España se está convirtiendo una patología emergente debido al aumento de la población inmigrante (AU)

Case Report: 24-year-old male from Equatorial Guinea income for treatment- resistant pulmonary tuberculosis. He referred eye discomfort. Ancillary tests revealed strong eosinophilia. He was sent for consultation because of large strange body sensation in the left eye, especially at night. Ophthalmic examination showed episcleral and conjunctival hyperemia and the presence of an adult worm under the conjunctiva, which was removed in surgery. Due to the high suspicion of loiasis we took blood samples for cultivation which confirmed the presence of microfilariae. After he recovered of his lung disease we scheduled systemic therapy against Loa-loa. Discussion: we must emphasize that ocular loiasis is a fairly common parasite infection in endemic areas of central Africa, but in Spain is becoming an emerging pathology due to the increase in the immigrant population (AU)

Humanos , Masculino , Adulto Jovem , Loíase/complicações , Loíase/diagnóstico , Loíase/parasitologia , Eosinofilia/diagnóstico , Eosinofilia/parasitologia , Loíase/induzido quimicamente , Loíase/patologia , Loíase/cirurgia , Eosinofilia/complicações , Eosinofilia/prevenção & controle
Exp Lung Res ; 39(9): 365-78, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24102347


Obesity is an important risk factor for asthma but the mechanistic basis for this association is not well understood. In the current study, the impact of obesity on lung inflammatory responses after allergen exposure was investigated. C57BL/6 mice maintained on a high-fat diet (HFD) or a normal diet (ND) after weaning were sensitized and challenged with cockroach allergen (CRA). Airway inflammation was assessed based on inflammatory cell recruitment, measurement of lung Th1-Th2 cytokines, chemokines, eicosanoids, and other proinflammatory mediators as well as airway hyperresponsiveness (AHR). CRA-challenged mice fed a HFD exhibited significantly decreased allergen-induced airway eosinophilia along with reduced lung IL-5, IL-13, LTC4, CCL11, and CCL2 levels as well as reduced mucus secretion and smooth muscle mass compared to ND fed mice. However, allergen-challenged HFD fed mice demonstrated significantly increased PAI-1 and reduced PGE2 levels in the lung relative to corresponding ND fed mice. Interestingly, saline-exposed HFD fed mice demonstrated elevated baseline levels of TGF-ß1, arginase-1, hypoxia-inducible factor-1α, and lung collagen expression associated with decreased lung function compared to corresponding ND fed mice. These studies indicate that a HFD inhibits airway eosinophilia while altering levels of PAI-1 and PGE2 in response to CRA in mice. Further, a HFD can lead to the development of lung fibrosis even in the absence of allergen exposure which could be due to innate elevated levels of specific profibrotic factors, potentially affecting lung function during asthma.

Alérgenos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Eosinofilia/prevenção & controle , Fibrose Pulmonar/etiologia , Doenças Respiratórias/prevenção & controle , Animais , Arginase/metabolismo , Asma/etiologia , Asma/imunologia , Hiper-Reatividade Brônquica/imunologia , Quimiocinas/metabolismo , Baratas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Eicosanoides/metabolismo , Eosinofilia/imunologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/imunologia , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Doenças Respiratórias/imunologia , Fatores de Risco , Serpina E2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
Fitoterapia ; 91: 298-304, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24060907


The aim of the study was to investigate the anti-asthmatic effects of apigenin and the possible mechanisms. Asthma model was established by ovalbumin-induced asthma. A total of 50 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg) and apigenin (5 mg/kg, 10 mg/kg). Airway resistance (Raw) was measured, histological studies were evaluated by hematoxylin and eosin (HE) staining, OVA-specific serum and BALF IgE levels and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), Th17 cells were evaluated by flow cytometry (FCM), and protein level of RORγt was measured by western blotting. Our study demonstrated that apigenin inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-6, TNF- and IL-17A levels were recovered. Histological studies demonstrated that apigenin substantially inhibited OVA-induced eosinophilia in lung tissue and airway tissue. Flow cytometry studies demonstrated that apigenin substantially inhibited Th17 cells. Western blotting studies demonstrated that apigenin substantially inhibited RORγt protein level. These findings suggest that apigenin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

Resistência das Vias Respiratórias/efeitos dos fármacos , Antiasmáticos/uso terapêutico , Apigenina/uso terapêutico , Asma/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Células Th17/metabolismo , Animais , Antiasmáticos/farmacologia , Apigenina/farmacologia , Asma/induzido quimicamente , Asma/metabolismo , Citocinas/metabolismo , Eosinofilia/metabolismo , Eosinofilia/prevenção & controle , Eosinófilos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ovalbumina , Extratos Vegetais/farmacologia
Pediatr. catalan ; 73(3): 102-106, jul.-sept. 2013. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-116848


Fundamento. La eosinofilia es un hallazgo frecuente en pediatría y puede deberse a múltiples causas. En nuestro medio, los procesos Eosinofília: experiència en una consulta de patologia importada en un centre de tercer nivell Míriam Poblet-Puig 1, Maria Espiau 1, Andrea Martín-Nalda 1, Pere Soler-Palacín 1, Elena Sulleiro 2, Concepció Figueras 1 1 Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria; 2 Servei de Microbiologia. Hospital Universitari Vall d’Hebron. Universitat Autònoma de Barcelona. Barcelona alérgicos (dermatitis atópica, asma y rinitis) son más frecuentes entre la población autóctona, y los procesos infecciosos, más frecuentes entre la población inmigrante. Objetivo. Describir las características de los pacientes estudiados por eosinofilia en una consulta de patología importada de pediatría. Método. Estudio descriptivo retrospectivo de los pacientes con eosinofilia en la consulta entre enero de 2009 y diciembre de 2010. Resultados. Se han incluido 39 pacientes. El 79,5% eran extranjeros. El 69,2% de los pacientes presentaban eosinofilia leve; el 25,7%, moderada, y el 5,1%, grave. Se llegó al diagnóstico etiológico de eosinofilia en el 59% de los casos (65,2% infección parasitaria, 26,1% atòpia, 8,7% otras causas). A todos los pacientes a los que se llegó a un diagnóstico etiológico se les administró tratamiento específico, observándose una disminución de la eosinofilia en el 93%. La zona de procedencia se asoció de forma estadísticamente significativa a los distintos diagnósticos etiológicos (p<0,05), siendo las infecciones parasitarias más frecuentes entre la población inmigrante (prevalencia del 72,2%), sin poder relacionar ninguna especie parasitaria con un área geográfica específica. No se encontró asociación entre el tiempo de estancia en el país de origen y la probabilidad de tener un resultado positivo en el coproparasitológico. Conclusiones. La eosinofilia es frecuente y debe ser estudiada incluso cuando se presenta de forma aislada, ya que puede ser la única manifestación de entidades potencialmente graves. Es importante aplicar un protocolo diagnóstico específico según procedencia y características del paciente (AU)

Background. Eosinophilia is a common laboratory finding among the pediatric population and may have multiple causes. Allergic disorders (most frequent among autochthonous population) and infectious diseases (more prevalent among immigrant patients) are considered to be the main etiologies. Objective. To determine the characteristics of patients with eosinophilia who were seen at an Imported Diseases Unit in a pediatric tertiary care hospital. Method. Descriptive retrospective study including all patients presenting with eosinophilia in the unit between January 2009 and December 2010. Results. Thirty-nine patients were included; 79.5% of them were immigrants. Sixty-nine point five percent had mild eosinophilia, 25.6% moderate, and 5.1% severe. A final diagnosis was reached in 59% of the cases (65.2% parasitic infection, 26.1% atopic disease, and 8.7% other causes). All patients with a final diagnosis received directed therapy. Among those, regression of the eosinophilia was observed in 93.3%. The area of origin was significantly associated with the final diagnosis (p<0.05); a higher prevalence of parasitic infections was found among immigrants (72.2%) than among native children. None of the parasitic species were found to correlate with a specific region. The time spent in the country of origin was not significantly associated with the probability of having a stool sample positive for parasites. Conclusions. Eosinophilia is a common finding that needs to be investigated, even when isolated, as it may be the first and only manifestation of a potentially severe condition. It is important to follow specific diagnostic protocols depending on the origin and characteristics of the patient (AU)

Humanos , Masculino , Feminino , Criança , Eosinofilia/epidemiologia , Eosinofilia/patologia , Eosinofilia/prevenção & controle , Emigrantes e Imigrantes/estatística & dados numéricos , Hospitais Universitários , Estudos Retrospectivos
Am J Respir Cell Mol Biol ; 48(2): 212-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23204391


Key features of asthma include bronchial hyperresponsiveness (BHR), eosinophilic airway inflammation, and bronchial remodeling, characterized by subepithelial collagen deposition, airway fibrosis, and increased bronchial smooth muscle (BSM) mass. The calcium-activated K(+) channel K(Ca)3.1 is expressed by many cells implicated in the pathogenesis of asthma, and is involved in both inflammatory and remodeling responses in a number of tissues. The specific K(Ca)3.1 blocker 5-[(2-chlorophenyl)(diphenyl)methyl]-1H-pyrazole (TRAM-34) attenuates BSM cell proliferation, and both mast cell and fibrocyte recruitment in vitro. We aimed to examine the effects of K(Ca)3.1 blockade on BSM remodeling, airway inflammation, and BHR in a murine model of chronic asthma. BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) on Days 0 and 14, and then challenged with intranasal OVA during Days 14-75. OVA-sensitized/challenged mice received TRAM-34 (120 mg/kg/day, subcutaneous) from Days -7 to 75 (combined treatment), Days -7 to 20 (preventive treatment), or Days 21 to 75 (curative treatment). Untreated mice received daily injections of vehicle (n = 8 per group). Bronchial remodeling was assessed by histological and immunohistochemical analyses. Inflammation was evaluated using bronchoalveolar lavage and flow cytometry. We also determined BHR in both conscious and anesthetized mice via plethysmography. We demonstrated that curative treatment with TRAM-34 abolishes BSM remodeling and subbasement collagen deposition, and attenuates airway eosinophilia. Although curative treatment alone did not significantly reduce BHR, the combined treatment attenuated nonspecific BHR to methacholine. This study indicates that K(Ca)3.1 blockade could provide a new therapeutic strategy in asthma.

Remodelação das Vias Aéreas/efeitos dos fármacos , Modelos Animais de Doenças , Eosinofilia/prevenção & controle , Canais de Potássio Cálcio-Ativados/antagonistas & inibidores , Pirazóis/farmacologia , Animais , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C