Spyros A Papiris1, Ioannis P Tomos2, Anna Karakatsani3, Aris Spathis4, Ioanna Korbila5, Antonis Analitis6, Likurgos Kolilekas7, Konstantinos Kagouridis8, Stylianos Loukides9, Petros Karakitsos10, Effrosyni D Manali11. 1. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: papiris@otenet.gr. 2. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: etomos@hotmail.com. 3. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: annakara@otenet.gr. 4. Department of Cytopathology, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: aspathis@med.uoa.gr. 5. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: ikorbila@gmail.com. 6. Department of Hygiene, School of Medicine, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: aanalitis@gmail.com. 7. 7th Pulmonary Department and Asthma Center, "Sotiria" Hospital for Chest Diseases, Athens, Greece. Electronic address: lykol@yahoo.gr. 8. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: konstantinos.kagouridis@gmail.com. 9. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: ssat@hol.gr. 10. Department of Cytopathology, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: pkaraki@med.uoa.gr. 11. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. Electronic address: fmanali@otenet.gr.
Abstract
INTRODUCTION: Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients. METHODS: Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied. RESULTS: Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines. CONCLUSION: High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-β, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.
INTRODUCTION: Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients. METHODS: Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied. RESULTS: Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines. CONCLUSION: High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-β, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.
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