BACKGROUND: The prognosis of idiopathic pulmonary fibrosis (IPF/UIP) is poor and its immunopathogenesis is insufficiently understood. OBJECTIVES: The aim of our study was to elucidate the compartmentalization of cell activation and the influence of corticosteroid therapy upon this activation in IPF/UIP. We determined the concentrations of proinflammatory cytokines released by bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMNC) in treated and untreated patients with IPF/UIP. We chose tumor necrosis factor-alpha (TNFalpha) since it is a cytokine predominantly secreted by cells of the monocyte/macrophage lineage and interleukin-2 (IL-2) exclusively by T lymphocytes. METHODS: The release of TNFalpha and IL-2 by BAL cells and PBMNC was measured in cell culture supernatants of 72 treated and untreated IPF/UIP patients. Additionally, in the blood compartment serological parameters reflecting the monocyte/macrophage and lymphocyte activation, such as neopterin and soluble IL-2 receptor (sIL-2R), were determined. RESULTS: The TNFalpha release by BAL cells was significantly elevated in both groups compared to controls but did not differ between treated and untreated patients with IPF/UIP. In 7 of 19 untreated patients with IPF, PBMNC were activated and released increased amounts of TNFalpha. In only 1 of 17 treated patients with IPF, TNFalpha release by PBMNC could be found. The serum level of neopterin, a marker of cell activation of the monocyte/macrophage lineage did not differ between treated and untreated patients. The BAL lymphocyte and PBMNC IL-2 release was significantly elevated in IPF/UIP patients without therapy compared to controls (p < 0.05). In contrast, no IL-2 release of BAL cells or PBMNC was observed in treated IPF/UIP patients. Lymphocyte activation was furthermore identified in untreated IPF patients by elevated soluble IL-2 receptor serum concentrations (p < 0.0001). CONCLUSIONS: Cells of the monocyte/macrophage lineage and T lymphocytes are activated in BAL cells and PBMNC of patients with IPF/UIP. During treatment, the systemic and local activation of T cells is suppressed. BAL macrophages, however, maintain their activated status, which might be the cause for the frequent chronic progression of the disease. Copyright 2003 S. Karger AG, Basel
BACKGROUND: The prognosis of idiopathic pulmonary fibrosis (IPF/UIP) is poor and its immunopathogenesis is insufficiently understood. OBJECTIVES: The aim of our study was to elucidate the compartmentalization of cell activation and the influence of corticosteroid therapy upon this activation in IPF/UIP. We determined the concentrations of proinflammatory cytokines released by bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMNC) in treated and untreated patients with IPF/UIP. We chose tumor necrosis factor-alpha (TNFalpha) since it is a cytokine predominantly secreted by cells of the monocyte/macrophage lineage and interleukin-2 (IL-2) exclusively by T lymphocytes. METHODS: The release of TNFalpha and IL-2 by BAL cells and PBMNC was measured in cell culture supernatants of 72 treated and untreated IPF/UIP patients. Additionally, in the blood compartment serological parameters reflecting the monocyte/macrophage and lymphocyte activation, such as neopterin and soluble IL-2 receptor (sIL-2R), were determined. RESULTS: The TNFalpha release by BAL cells was significantly elevated in both groups compared to controls but did not differ between treated and untreated patients with IPF/UIP. In 7 of 19 untreated patients with IPF, PBMNC were activated and released increased amounts of TNFalpha. In only 1 of 17 treated patients with IPF, TNFalpha release by PBMNC could be found. The serum level of neopterin, a marker of cell activation of the monocyte/macrophage lineage did not differ between treated and untreated patients. The BAL lymphocyte and PBMNC IL-2 release was significantly elevated in IPF/UIP patients without therapy compared to controls (p < 0.05). In contrast, no IL-2 release of BAL cells or PBMNC was observed in treated IPF/UIP patients. Lymphocyte activation was furthermore identified in untreated IPF patients by elevated soluble IL-2 receptor serum concentrations (p < 0.0001). CONCLUSIONS: Cells of the monocyte/macrophage lineage and T lymphocytes are activated in BAL cells and PBMNC of patients with IPF/UIP. During treatment, the systemic and local activation of T cells is suppressed. BAL macrophages, however, maintain their activated status, which might be the cause for the frequent chronic progression of the disease. Copyright 2003 S. Karger AG, Basel
Authors: Ana P M Serezani; Bruno D Pascoalino; Julia M R Bazzano; Katherine N Vowell; Harikrishna Tanjore; Chase J Taylor; Carla L Calvi; A Scott McCall; Matthew D Bacchetta; Ciara M Shaver; Lorraine B Ware; Margaret L Salisbury; Nicholas E Banovich; Peggy L Kendall; Jonathan A Kropski; Timothy S Blackwell Journal: Am J Respir Cell Mol Biol Date: 2022-07 Impact factor: 7.748
Authors: Syed R Gilani; Louis J Vuga; Kathleen O Lindell; Kevin F Gibson; Jianmin Xue; Naftali Kaminski; Vincent G Valentine; Emily K Lindsay; M Patricia George; Chad Steele; Steven R Duncan Journal: PLoS One Date: 2010-01-29 Impact factor: 3.240
Authors: T Nagai; M Tanaka; K Hasui; H Shirahama; S Kitajima; S Yonezawa; B Xu; T Matsuyama Journal: Clin Exp Immunol Date: 2010-06-09 Impact factor: 5.732
Authors: Jianmin Xue; Bernadette R Gochuico; Ahmad Samer Alawad; Carol A Feghali-Bostwick; Imre Noth; Steven D Nathan; Glenn D Rosen; Ivan O Rosas; Sanja Dacic; Iclal Ocak; Carl R Fuhrman; Karen T Cuenco; Mary A Smith; Susan S Jacobs; Adriana Zeevi; Penelope A Morel; Joseph M Pilewski; Vincent G Valentine; Kevin F Gibson; Naftali Kaminski; Frank C Sciurba; Yingze Zhang; Steven R Duncan Journal: PLoS One Date: 2011-02-23 Impact factor: 3.240