Systemic immune cell activation in a subgroup of patients with idiopathic pulmonary fibrosis.
BACKGROUND
The prognosis of idiopathic pulmonary fibrosis (IPF/UIP) is poor and its immunopathogenesis is insufficiently understood.


OBJECTIVE
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.
Homolka
Jiri
J
Department of Pneumology, University Hospital Freiburg, Freiburg, Germany.
Ziegenhagen
Manfred W
MW
Gaede
Karoline I
KI
Entzian
Peter
P
Zissel
Gernot
G
Müller-Quernheim
Joachim
J
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha