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  • Title: Increased expression of proinflammatory chemokines in bronchoalveolar lavage cells of patients with progressing idiopathic pulmonary fibrosis and sarcoidosis.
    Author: Ziegenhagen MW, Schrum S, Zissel G, Zipfel PF, Schlaak M, Müller-Quernheim J.
    Journal: J Investig Med; 1998 Jun; 46(5):223-31. PubMed ID: 9676055.
    Abstract:
    BACKGROUND: There is increasing evidence that the proinflammatory chemokines interleukin-8 (IL-8) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are involved in the pathogenesis of interstitial lung diseases. METHODS: We investigated the release of TNF-alpha, IL-8, MIP-1 alpha by cultured bronchoalveolar lavage (BAL) immune cells of patients with idiopathic pulmonary fibrosis (IPF, n = 24), sarcoidosis (SAR, n = 24), and controls (n = 20) by ELISA. Furthermore, mRNA expression of these cytokines in BAL cells immediately frozen after bronchoscopy was determined. The clinical course of the disease was evaluated and the patients were subdivided into groups with progressing or stable disease. RESULTS: TNF-alpha, IL-8, and MIP-1 alpha were significantly elevated in the supernatants of BAL immune cells of IPF and SAR patients with progressing disease compared to controls (p < 0.005 in both diseases) and also when compared to patients with stable disease (IPF p < 0.005, SAR p < 0.05). Interestingly, the release of TNF-alpha, IL-8, and MIP-1 alpha did not differ significantly between IPF patients with stable disease and controls, whereas in SAR patients with stable disease a difference at a low significance level (p < 0.05) was obtained. In IPF and SAR patients with progressing disease, a clear mRNA signal of TNF-alpha, IL-8, and MIP-1 alpha was detected in BAL immune cells not having been stimulated by adherence to plastic, whereas in patients with stable disease or controls only a weak signal was observed. MIP-1 alpha release correlated positively with percentage of BAL eosinophils in IPF and SAR. Furthermore, the percentage of eosinophils in BAL was significantly elevated in the IPF subgroup with progressing disease. CONCLUSIONS: Our data demonstrate that an exaggerated expression of TNF-alpha, IL-8, and MIP-1 alpha in BAL immune cells is characteristic for IPF and SAR patients who show progressing disease.
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