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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Allergen-specific immunotherapy has been used for successful treatment of atopic diseases&#46; They may act by modifying the patterns of cytokines produced by T cells&#46; However&#44; the precise mechanism by which it accomplishes these effects is still incompletely understood&#46;</p> <span class="elsevierStyleSectionTitle">Objective</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">To evaluate the effect of one year immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in atopic patients&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">We studied 10 atopic patients sensitised to common environmental allergens receiving immunotherapy over one year mean period&#46; Six of these patients were studied before and after immunotherapy&#46; Fourteen atopic patients untreated and 7 non-atopic subjects were used as control groups&#46; Intracellular cytokine production &#40;IFN-&#947;&#59; IL-4&#59; IL- 5&#59; IL-10&#41; was determined by flow cytometry following stimulation with phorbol myristate acetate &#40;PMA&#41;&#44; ionomycin and brefeldin&#46; Mann-Whitney U and Wilcoxon non-parametric tests were utilized for the statistical analysis&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The expression of IL-4 and IL-5 in T cells&#44; characteristically increased in atopic patients&#44; respectively 13&#46;8 &#40;3&#46;1 &#8211; 31&#46;8&#41; and 6&#46;7&#37; &#40;1&#46;0 -20&#46;4&#41;&#44; was significantly lower in the immunotherapy group 5&#46;4 &#40;2&#46;9 -15&#46;6&#41; p&#61;0&#46;007 and 2&#46;1&#37; &#40;0&#44;6 &#8211; 4&#46;8&#41; p&#61;0&#46;035 and similar in the non-atopic control group&#46; The levels of IFN-&#947; did not differ between the studied groups but the ratio IFN-&#947; &#47; IL-4 produced by CD4&#43; T lymphocytes increased significantly in the patients receiving immunotherapy&#46; In addition&#44; there was an increase in the expression of IL-10 by T cells of the immunotherapy group compared to the non-atopic controls 1&#46;9 &#40;1&#46;0 &#8211; 4&#46;9&#41; versus 1&#46;4&#37; &#40;0&#46;9 &#8211; 1&#46;4&#41; p&#61;0&#46;02&#44; being more evident in CD8&#43; T lymphocytes&#46; IL-10 correlated significantly with all the profile T2 cytokines &#40;IL-4 and IL-5&#41; and with the phenotype Tc2&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">After one year of immunotherapy the peripheral T cells response to a polyclonal stimulation revealed a reduction in IL-4 and IL-5 production&#44; characteristically increased in atopic disease&#46; The increase of IL-10 that we found in our study suggested the existence of a profile T2 regulatory population&#44; more evident in CD8&#43;T lymphocytes&#46;</p>"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A coordena&#231;&#227;o das caracter&#237;sticas humorais e celulares da resposta al&#233;rgica&#44; sabe-se hoje&#44; est&#225; dependente da regula&#231;&#227;o por linf&#243;citos T&#46; As vacinas de alerg&#233;nios s&#227;o uma terap&#234;utica que consegue modular a resposta das c&#233;lulas T&#44; e cujos mecanismos imunol&#243;gicos permanecem incompletamente esclarecidos&#46;</p> <span class="elsevierStyleSectionTitle">Objectivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar o efeito da imunoterapia&#44; ap&#243;s um ano de tratamento&#44; na express&#227;o de citocinas de perfil T1 e T2 em linf&#243;citos de sangue perif&#233;rico de doentes at&#243;picos&#46;</p> <span class="elsevierStyleSectionTitle">Material e m&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudaram-se dez doentes at&#243;picos sensibilizados a aeroalerg&#233;nios comuns a fazerem vacinas de alerg&#233;nios num per&#237;odo m&#233;dio de um ano&#46; Dentre estes&#44; seis foram estudados antes e ap&#243;s a vacina&#46; Como controlo estudou-se um grupo at&#243;pico sem imunoterapia constitu&#237;do por 14 doentes tamb&#233;m sensibilizados a aeroalerg&#233;nios comuns e um grupo de indiv&#237;duos n&#227;o at&#243;picos&#44; saud&#225;veis&#44; constitu&#237;do por 7 elementos&#46; A activa&#231;&#227;o dos linf&#243;citos T fez-se com PMA&#44; ionomicina e brefeldina e estudaram-se as citocinas intracitoplasm&#225;ticas IFN-&#947;&#44; IL-4&#44; IL-5 e IL-10 por citometria de fluxo&#46; Procedeu-se a an&#225;lise estat&#237;stica por testes n&#227;o param&#233;tricos &#40;Teste de Mann-Whitney U e Wilcoxon&#41;&#44; considerando-se significativo p&#8804;0&#44;05&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A express&#227;o de IL-4 e IL-5 nas c&#233;lulas T&#44; caracteristicamente aumentada nos doentes at&#243;picos&#44; respectivamente 13&#44;8 &#40;3&#44;1-31&#44;8&#41; e 6&#44;7&#37; &#40;1&#44;0-20&#44;4&#41;&#44; &#233; significativamente mais baixa no grupo que realizou a imunoterapia 5&#44;4 &#40;2&#44;9-15&#44;6&#41; p&#61; 0&#44;007 e 2&#44;1&#37; &#40;0&#44;6-4&#44;8&#41; p&#61;0&#44;035 n&#227;o diferindo do grupo controlo n&#227;o at&#243;pico 5&#44;1 &#40;4&#44;1-6&#44;9&#41; e 1&#44;0 &#40;0&#44;4-2&#44;1&#41;&#46; Os n&#237;veis de IFN-&#947; n&#227;o variaram significativamente entre os tr&#234;s grupos estudados&#44; mas a raz&#227;o IFN-&#947;&#47; &#47;IL-4 nos linf&#243;citos T CD4 aumentou significativamente nos doentes submetidos a imunoterapia&#46; Por outro lado&#44; houve um aumento da express&#227;o de IL-10 nas c&#233;lulas T circulantes do grupo sob imunoterapia&#44; comparativamente a controlos n&#227;o at&#243;picos 1&#44;9 &#40;1&#44;0-4&#44;9&#41; <span class="elsevierStyleItalic">versus</span> 1&#44;4&#37; &#40;0&#44;9-1&#44;4&#41; p&#61;0&#44;02&#44; sendo mais evidente nos linf&#243;citos T CD8&#46; A IL-10 correlacionou-se de forma significativa com todas as citocinas de perfil T2 &#40;IL-4 e IL-5&#41; e com o fen&#243;tipo Tc2&#46;</p> <span class="elsevierStyleSectionTitle">Conclus&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Ap&#243;s um ano de imunoterapia&#44; a resposta das c&#233;lulas T do sangue perif&#233;rico a uma estimula&#231;&#227;o policlonal evidenciou uma diminui&#231;&#227;o da express&#227;o das citocinas &#40;IL-4 e IL-5&#41;&#44; caracteristicamente aumentadas na doen&#231;a al&#233;rgica&#46; O aumento da IL-10&#44; que tamb&#233;m verific&#225;mos&#44; sugere a exist&#234;ncia de uma popula&#231;&#227;o reguladora de perfil T2&#44; sendo mais evidente nos linf&#243;citos T CD8&#46;</p>"
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Specific immunotherapy effect on peripheral blood T1/T2 lymphocytes in atopic patients
Repercussão da imunoterapia específica na população T1 e T2 de linfócitos periféricos em doentes atópicos
Manuela Rebordão1,6, Luís Delgado2,6, Helena Pinto3,6, Augusto Remédios4,6, L. Taborda-Barata5,6
1 Técnica Superior de Saúde. Assistente principal. Serviço de Análises Clínicas do Hospital Militar de Belém/Senior Health Technician. Senior assistant. Belém Military Hospital Analysis Clinic
2 Professor Associadoda Faculdade de Medicina da Universidade do Porto. Serviço e Laboratório de Imunologia, Faculdade de Medicina da Universidade do Porto, Hospital de São João, Porto/Associate Professor at Porto University Medical School. Immunology Unit and Laboratory, Porto University Medical School, Hospital de São João, Porto
3 Tenente-coronel médica – Directora do Serviço de Pneumologia do Hospital Militar de Belém/Medical Lieutenant Colonel – Director of Pulmonology Unit, Belém Military Hospital
4 Tenente-coronel farmacêutico – Director do Serviço de Análises Clínicas do Hospital Militar de Belém/Pharmacist Lieutenant Colonel – Director of Analysis Clinic, Belém Military Hospital
5 Professor Auxiliar de imunologia clínica, Faculdade de Ciências da Saúde, Universidade da Beira Interior. Director do Serviço de Imunoalergologia do Hospital
6 Pêro Covilhã/Assistant Professor Immunology Unit, Beira Interior University Health Sciences School. Immunoallergologist, Director of Immunoallergology Unit, Pêro Covilhã Hospital
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Allergen-specific immunotherapy has been used for successful treatment of atopic diseases&#46; They may act by modifying the patterns of cytokines produced by T cells&#46; However&#44; the precise mechanism by which it accomplishes these effects is still incompletely understood&#46;</p> <span class="elsevierStyleSectionTitle">Objective</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">To evaluate the effect of one year immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in atopic patients&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">We studied 10 atopic patients sensitised to common environmental allergens receiving immunotherapy over one year mean period&#46; Six of these patients were studied before and after immunotherapy&#46; Fourteen atopic patients untreated and 7 non-atopic subjects were used as control groups&#46; Intracellular cytokine production &#40;IFN-&#947;&#59; IL-4&#59; IL- 5&#59; IL-10&#41; was determined by flow cytometry following stimulation with phorbol myristate acetate &#40;PMA&#41;&#44; ionomycin and brefeldin&#46; Mann-Whitney U and Wilcoxon non-parametric tests were utilized for the statistical analysis&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The expression of IL-4 and IL-5 in T cells&#44; characteristically increased in atopic patients&#44; respectively 13&#46;8 &#40;3&#46;1 &#8211; 31&#46;8&#41; and 6&#46;7&#37; &#40;1&#46;0 -20&#46;4&#41;&#44; was significantly lower in the immunotherapy group 5&#46;4 &#40;2&#46;9 -15&#46;6&#41; p&#61;0&#46;007 and 2&#46;1&#37; &#40;0&#44;6 &#8211; 4&#46;8&#41; p&#61;0&#46;035 and similar in the non-atopic control group&#46; The levels of IFN-&#947; did not differ between the studied groups but the ratio IFN-&#947; &#47; IL-4 produced by CD4&#43; T lymphocytes increased significantly in the patients receiving immunotherapy&#46; In addition&#44; there was an increase in the expression of IL-10 by T cells of the immunotherapy group compared to the non-atopic controls 1&#46;9 &#40;1&#46;0 &#8211; 4&#46;9&#41; versus 1&#46;4&#37; &#40;0&#46;9 &#8211; 1&#46;4&#41; p&#61;0&#46;02&#44; being more evident in CD8&#43; T lymphocytes&#46; IL-10 correlated significantly with all the profile T2 cytokines &#40;IL-4 and IL-5&#41; and with the phenotype Tc2&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">After one year of immunotherapy the peripheral T cells response to a polyclonal stimulation revealed a reduction in IL-4 and IL-5 production&#44; characteristically increased in atopic disease&#46; The increase of IL-10 that we found in our study suggested the existence of a profile T2 regulatory population&#44; more evident in CD8&#43;T lymphocytes&#46;</p>"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A coordena&#231;&#227;o das caracter&#237;sticas humorais e celulares da resposta al&#233;rgica&#44; sabe-se hoje&#44; est&#225; dependente da regula&#231;&#227;o por linf&#243;citos T&#46; As vacinas de alerg&#233;nios s&#227;o uma terap&#234;utica que consegue modular a resposta das c&#233;lulas T&#44; e cujos mecanismos imunol&#243;gicos permanecem incompletamente esclarecidos&#46;</p> <span class="elsevierStyleSectionTitle">Objectivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar o efeito da imunoterapia&#44; ap&#243;s um ano de tratamento&#44; na express&#227;o de citocinas de perfil T1 e T2 em linf&#243;citos de sangue perif&#233;rico de doentes at&#243;picos&#46;</p> <span class="elsevierStyleSectionTitle">Material e m&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudaram-se dez doentes at&#243;picos sensibilizados a aeroalerg&#233;nios comuns a fazerem vacinas de alerg&#233;nios num per&#237;odo m&#233;dio de um ano&#46; Dentre estes&#44; seis foram estudados antes e ap&#243;s a vacina&#46; Como controlo estudou-se um grupo at&#243;pico sem imunoterapia constitu&#237;do por 14 doentes tamb&#233;m sensibilizados a aeroalerg&#233;nios comuns e um grupo de indiv&#237;duos n&#227;o at&#243;picos&#44; saud&#225;veis&#44; constitu&#237;do por 7 elementos&#46; A activa&#231;&#227;o dos linf&#243;citos T fez-se com PMA&#44; ionomicina e brefeldina e estudaram-se as citocinas intracitoplasm&#225;ticas IFN-&#947;&#44; IL-4&#44; IL-5 e IL-10 por citometria de fluxo&#46; Procedeu-se a an&#225;lise estat&#237;stica por testes n&#227;o param&#233;tricos &#40;Teste de Mann-Whitney U e Wilcoxon&#41;&#44; considerando-se significativo p&#8804;0&#44;05&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A express&#227;o de IL-4 e IL-5 nas c&#233;lulas T&#44; caracteristicamente aumentada nos doentes at&#243;picos&#44; respectivamente 13&#44;8 &#40;3&#44;1-31&#44;8&#41; e 6&#44;7&#37; &#40;1&#44;0-20&#44;4&#41;&#44; &#233; significativamente mais baixa no grupo que realizou a imunoterapia 5&#44;4 &#40;2&#44;9-15&#44;6&#41; p&#61; 0&#44;007 e 2&#44;1&#37; &#40;0&#44;6-4&#44;8&#41; p&#61;0&#44;035 n&#227;o diferindo do grupo controlo n&#227;o at&#243;pico 5&#44;1 &#40;4&#44;1-6&#44;9&#41; e 1&#44;0 &#40;0&#44;4-2&#44;1&#41;&#46; Os n&#237;veis de IFN-&#947; n&#227;o variaram significativamente entre os tr&#234;s grupos estudados&#44; mas a raz&#227;o IFN-&#947;&#47; &#47;IL-4 nos linf&#243;citos T CD4 aumentou significativamente nos doentes submetidos a imunoterapia&#46; Por outro lado&#44; houve um aumento da express&#227;o de IL-10 nas c&#233;lulas T circulantes do grupo sob imunoterapia&#44; comparativamente a controlos n&#227;o at&#243;picos 1&#44;9 &#40;1&#44;0-4&#44;9&#41; <span class="elsevierStyleItalic">versus</span> 1&#44;4&#37; &#40;0&#44;9-1&#44;4&#41; p&#61;0&#44;02&#44; sendo mais evidente nos linf&#243;citos T CD8&#46; A IL-10 correlacionou-se de forma significativa com todas as citocinas de perfil T2 &#40;IL-4 e IL-5&#41; e com o fen&#243;tipo Tc2&#46;</p> <span class="elsevierStyleSectionTitle">Conclus&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Ap&#243;s um ano de imunoterapia&#44; a resposta das c&#233;lulas T do sangue perif&#233;rico a uma estimula&#231;&#227;o policlonal evidenciou uma diminui&#231;&#227;o da express&#227;o das citocinas &#40;IL-4 e IL-5&#41;&#44; caracteristicamente aumentadas na doen&#231;a al&#233;rgica&#46; O aumento da IL-10&#44; que tamb&#233;m verific&#225;mos&#44; sugere a exist&#234;ncia de uma popula&#231;&#227;o reguladora de perfil T2&#44; sendo mais evidente nos linf&#243;citos T CD8&#46;</p>"
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Pulmonology

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