RESUMO
BACKGROUND: ADAM28, ADAM33, IL-13, IL-4 and other cytokines (IL-6 and IL-10) seem to play important roles in the persistence and maintenance of acute inflammatory processes that ultimately lead to lung remodeling and pulmonary fibrosis, which may be responsible for the high morbidity and mortality rates associated with non-pandemic acute viral pneumonias in childhood. OBJECTIVES: The aim of this study was to evaluate the roles of ADAM33, ADAM28, IL4, IL6, IL10 and IL13 in the development of inflammation and alveolar fibrosis due to lethal acute respiratory infections of the lower airway in a pediatric population, especially in those with viral etiology. STUDY DESIGN: For this study, 193 cases were selected, and samples from the cases were processed for viral antigen detection by immunohistochemistry and then separated into two groups: virus-positive (n=68) and virus-negative (n=125). Immunohistochemistry was performed to assess the presence of metalloproteinases (ADAM33 and ADAM28) and inflammatory cytokines (IL-4, IL-13, IL-6, IL-10) in the alveolar septa. RESULTS: The virus-positive group showed stronger immunolabeling for ADAM33, ADAM28, IL-4 and IL-13 (p<0.0001 for all variables). The staining intensities for ADAM33 and ADAM28 were directly proportional to the intensities for IL-4 and IL-13 (p<0.0001). CONCLUSIONS: The results of this study suggest that these proteins play important roles in pulmonary inflammatory reactions elicited against etiological viral agents. In addition, these mediators may affect the process of lung remodeling and the development of pulmonary fibrosis.
Assuntos
Proteínas ADAM/análise , Lesão Pulmonar Aguda/patologia , Interleucina-13/análise , Interleucina-4/análise , Pneumonia Viral/patologia , Lesão Pulmonar Aguda/imunologia , Antígenos Virais/análise , Pré-Escolar , Feminino , Fibrose/patologia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Pulmão/patologia , Masculino , Pneumonia Viral/imunologiaRESUMO
JUSTIFICATIVA E OBJETIVOS: Estudos com novas terapias utilizando transplante autólogo de infiltrado linfocitário têm mostrado resultados promissores no tratamento de melanomas, justificando pesquisas nesta área. O objetivo deste estudo foi avaliar a expressão fenotípica do infiltrado linfocitário tumoral (TIL), através de marcadores imuno-histoquímicos de moléculas de superfície de células inflamatórias em melanomas cutâneos primários e estudar a sua correlação com outros fatores prognósticos já estabelecidos. MÉTODO: Análise da infiltração linfocitária tumoral em 43 melanomas primários utilizando técnicas de imuno-histoquímica (anticorpos anti-CD3, CD20, CD4, CD8, CD25 e anti-CD57). As variáveis prognósticas foram: clínicas (idade, sexo, localização, metástases e evolução) e anatomopatológicas: Breslow (se fino = < 1 mm = 21 casos ou grosso > 1 mm = 22 casos), nível de Clark, número de mitoses, ulceração, regressão, satelitose e tipo TIL (caso brisk ou nonbrisk). RESULTADOS: Os tumores finos apresentaram maior concentração de linfócitos TCD4+ (p = 0,01) e CD57+ (p = 0,008). Os tumores de cabeça-tronco-pescoço apresentam predomínio de linfócitos TCD8+ e de TCD25+ (p = 0,02). CONCLUSÃO: Tumores centrais, que geralmente são de pior prognóstico, apresentaram maior resposta imune humoral (predomínio de linfócitos CD20+) e são a forma mais prevalente no sexo masculino. Os tumores grossos, que são de pior prognóstico, estavam associados com o padrão nonbrisk de TIL, com maior taxa de mitoses, com maior incidência de satelitoses e com predomínio de ulceração. A presença de ulceração ocorreu em maior número de vezes em pacientes com faixa etária mais elevada. Os tumores finos, que são de melhor prognóstico, apresentaram maior resposta imune celular (predomínio de linfócitos CD4+ e CD57+).
BACKGROUND AND OBJECTIVES: Studies of new therapies that use lymphocytic infiltrate autologous transplantation have shown promising results for the treatment of melanomas, warranting researches in this area. The objective of this study was to assess the phenotypic expression of tumor-infiltrating lymphocytes through immunohistochemical markers of surface molecules of inflammatory cells in primary cutaneous melanomas, and to study its correlation with other established prognostic factors. METHOD: Tumor lymphocytic infiltration analysis in 43 primary melanomas using immunohistochemical techniques (CD3, CD20, CD4, CD8, CD25 and CD57 antibodies). The prognostic variables were: clinical (age, sex, location, metastases and evolution) and anatomopathological variables: Breslow thickness (if thin = < 1 mm = 21 cases or thick > 1 mm = 22 cases), Clark level, number of mitoses, ulceration, regression, satellitosis and type of TIL (if brisk or nonbrisk). RESULTS: The thin tumors showed higher concentration of CD4+ (p = 0.01) and CD57+ (p = 0.008) T lymphocytes. The head-trunk-neck tumors exhibit a predominance of CD8 and CD25 (p = 0.02) T lymphocytes. CONCLUSION: Central tumors, which generally have poorer prognosis, had a higher humoral immune response (CD20 lymphocyte predominance) and are the most prevalent form in males. The thick tumors, which have worse prognosis, were associated with the non-brisk pattern of TIL with a higher rate of mitosis, a higher incidence of satelitoses and ulceration predominance. The presence of ulceration occurred more often in older patients. The thin tumors, which have the best prognosis, had a higher cellular immune response (predominance of CD4+ and CD57+ lymphocytes).