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.

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.

Immunohistochemistry analysis of pulmonary infiltrates in necropsy samples of children with non-pandemic lethal respiratory infections (RSV; ADV; PIV1; PIV2; PIV3; FLU A; FLU B).

BACKGROUND: Acute viral respiratory infections represent a globally important cause of morbidity and mortality in childhood. An individual's cellular response appears to play a critical role in recovery from infections, given that individuals with impaired cellular immunity, congenital or acquired, have more severe diseases and secrete the virus for longer periods. OBJECTIVES: The aim of this study was to immunohistochemically evaluate the expression of the cell surface antigens CD4, CD8, CD25, CD14 and CD74, in pneumonic infiltrates in the alveolar septa using paraffin-embedded lung samples from autopsies of immunocompetent children who died of lethal, non-pandemic, severe acute respiratory infections. STUDY DESIGN: From 794 cases of pediatric autopsies of patients with severe respiratory disease (between 1960 and 2004), 193 cases were selected for this study. To identify subpopulations of inflammatory cells in the alveolar septa, cell surface antigen expression was assessed by immunohistochemistry using the following primary antibodies: anti-CD4, anti-CD8, anti-CD14, anti-CD25 and anti-CD74. RESULTS: The TCD8+ lymphocyte count was higher in the virus-positive group (p = 0.04) and was also much higher among cases that were positive for more than three viral types (p = 0.016). There were fewer CD14+ cells in cases of AdV (adenovirus) infection (p = 0.002), and there was a predominance of CD74+ cells in the histopathological pattern defined as interstitial pneumonitis (p = 0.037). CONCLUSIONS: The results of this study demonstrate that TCD8+ lymphocytes present in the alveolar septa participate to a greater extent in the response toward viral pneumonia, while CD14+ cell numbers are often reduced in cases of AdV.