INCREASED EXPRESSION OF PROINFLAMMATORY CHEMOKINES IN BRONCHOALVEOLARLAVAGE CELLS OF PATIENTS WITH PROGRESSING IDIOPATHIC PULMONARY FIBROSIS AND SARCOIDOSIS

Background: There is increasing evidence that the proinflammatory chem okines interleukin-8 (IL-8) and macrophage inflammatory protein-1 alph a. (MIP-1 alpha) are involved in the pathogenesis of interstitial lung diseases. Methods: We investigated the release of TNF-alpha, IL-8, MI P-1 alpha by cultured bronchoalveolar lavage (BAL) immune cells of pat ients with idiopathic pulmonary fibrosis (IPF, n = 24), sarcoidosis (S AR, n = 24), and controls (n = 20) by ELISA. Furthermore, mRNA express ion of these cytokines in BAL cells immediately frozen after bronchosc opy was determined. The clinical course of the disease was evaluated a nd 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 patie nts with progressing disease compared to controls (p < 0.005 in both d iseases) 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 wi th stable disease and controls, whereas in SAR patients with stable di sease a difference at a low significance level (p < 0.05) was obtained . In IPF and SAR patients with progressing disease, a clear mRNA signa l 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 patien ts with stable disease or controls only a weak signal was observed. MI P-1 alpha release correlated positively with percentage of BAL eosinop hils in IPF and SAR. Furthermore, the percentage of eosinophils in BAL was significantly elevated in the IPF subgroup with progressing disea se. Conclusions: Our data demonstrate that an exaggerated expression o f TNF-alpha, IL-8, and MIP-1 alpha in BAL immune cells is characterist ic for IPF and SAR patients who show progressing disease.