title: The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil. Electronic address: lnno@terra.com.br.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Baurakiades
authors.affiliation: Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil. Electronic address: victor.costajr@gmail.com.
authors.forename: Victor Horácio
authors.initials: VH
authors.lastname: Costa
authors.affiliation: Hospital de Clínicas of Federal University of Paraná, Rua General Carneiro, 181, Centro, Curitiba, Paraná, Brazil. Electronic address: sraboni@ufpr.br.
authors.forename: Sonia Mara
authors.initials: SM
authors.lastname: Raboni
authors.affiliation: Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil. Electronic address: vivi.telli@hotmail.com.
authors.forename: Vivian Rafaela Telli
authors.initials: VR
authors.lastname: de Almeida
authors.affiliation: Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil. Electronic address: kskl@onda.com.br.
authors.forename: Kelly Susana Kunze
authors.initials: KS
authors.lastname: Larsen
authors.affiliation: Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil. Electronic address: jnk@gmail.com.
authors.forename: Juliana Nemetz
authors.initials: JN
authors.lastname: Kohler
authors.affiliation: Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil. Electronic address: priscillagozzo@hotmail.com.
authors.forename: Priscilla do Carmo
authors.initials: Pdo C
authors.lastname: Gozzo
authors.affiliation: Federal University of Paraná, Rua General Carneiro, 181, Centro, Curitiba, Paraná, Brazil. Electronic address: giseli@ufpr.br.
authors.forename: Giseli
authors.initials: G
authors.lastname: Klassen
authors.affiliation: Federal University of Paraná, Rua General Carneiro, 181, Centro, Curitiba, Paraná, Brazil. Electronic address: gracimanica@hotmail.com.
authors.forename: Graciele C M
authors.initials: GC
authors.lastname: Manica
authors.affiliation: Pontifical Catholic University of Paraná, Rua Imaculada Conceição, 1155, Prado Velho, Curitiba, Paraná, Brazil. Electronic address: lnno@terra.com.br.
authors.forename: Lucia
authors.initials: L
authors.lastname: de Noronha
mesh_terms: D051722:ADAM Proteins / Q000032:analysis*; D055371:Acute Lung Injury / Q000276:immunology / Q000473:pathology*; D000956:Antigens, Viral / Q000032:analysis; D002675:Child, Preschool; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000032:analysis*; D015847:Interleukin-4 / Q000032:analysis*; D008168:Lung / Q000473:pathology; D008297:Male; D011024:Pneumonia, Viral / Q000276:immunology / Q000473:pathology*
chemical_list: D000956:Antigens, Viral; C578095:IL13 protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; D015847:Interleukin-4; D051722:ADAM Proteins; C410224:ADAM28 protein, human; C450441:ADAM33 protein, human
keywords: ADAM28; ADAM33; IL-13; IL-4; Pneumonia; Virus