Polymorphisms in the IL-1 receptor antagonist gene (IL1RN) and TNF have been associated with susceptibility to IPF
[6,7]. Several studies suggest that IL-1β and IL-1Ra play a critical role in bleomycin-induced fibrosis in mice. Rucaparib cost Fibrosis is induced by IL-1β and neutralization of IL-1β by antibodies or specific blockage of the receptor IL-1R1 reduces the development of fibrosis [8]. In normal homeostasis, IL-1Ra production by alveolar macrophages is higher than the production of IL-1β. However, decrease in the ratio of IL-1Ra to IL-1β favours the augmentation of the pro-fibrotic function of IL-1β[9]. The aim of this study was to investigate both the predisposition and disease-modifying effects CX5461 of genetic variations in the IL1B and IL1RN genes and corresponding proinflammatory cytokine levels in serum and bronchoalveolar lavage fluid (BALF) in a cohort of IPF patients. Patients with IPF presenting at the Department of Pulmonology of the St Antonius Hospital in Nieuwegein between 1998 and 2007 were included in this study. From that time serum, BALF and DNA were collected from all interstitial lung disease (ILD) patients presented at our department after informed consent was given. These patients were enrolled in our database for scientific research. Retrospectively, the diagnosis of
IPF was reviewed and validated using current American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Diagnoses made before 2002 were reviewed by an experienced clinician (J.v.d.B., J.G.), and why patients were included only when current ATS/ERS criteria were met. Other causes of usual interstitial pneumonia (UIP) (drugs, collagen vascular diseases) were ruled out. Seventy-seven IPF patients [mean age 60·8 years, standard deviation (s.d.) 13·6, 58 males, 19 females] were included in the present study and donated DNA. In 54 of 77 cases serum and BALF samples were also available at the time of
diagnosis. At the time of serum sampling eight patients received low-dose oral corticosteroids. In 58 cases the diagnosis of UIP was confirmed on lung biopsy (75%). BALF was collected as described previously [10]. Samples were stored at −80°C until analysis. Median lung function parameters at the time of diagnosis were as follows: forced vital capacity (FVC) 75·7 % predicted [interquartile range (IQR) 61·7–87·3], DLCO 42·5 % predicted (IQR 33·1–55·6). The control group consisted of 349 healthy Caucasian volunteers (mean age 39·2 years, s.d. 12·4, 139 males, 210 females). In 36 cases in the control group, BAL was performed and in those controls cytokine levels in serum and BALF were measured. The study protocol was approved by the Ethical Committee of the St Antonius Hospital and all subjects gave written informed consent.