Thalidomide partially reduces IL-18, IL-8 and TNF- release from alveolar macrophages in interstitial lung disease

¹ Dept of Pneumology and Allergology, Ruhrlandklinik, Medical Faculty, University of Essen, Germany
² Dept of General Medicine and Clinical Investigation, Nara Medical University, Nara, Japan
³ Dept of Neurosciences, Faculty of Medicine and Dentistry, Basque Country University, Bilbao, Spain
⁴ Dept of General Medicine and Clinical Investigation, Nara Medical University, Nara, Japan; and General and Experimental Pathology, Ruhr University, Bochum, Germany

^* To whom correspondence should be addressed. E-mail: ERJ.costabel{at}t-online.de.

	Abstract

Thalidomide exerts diverse actions of anti-inflammation, immunomodulation and antiangiogenesis. The efficacy of thalidomide treatment in sarcoidosis with lupus pernio is thought to be due to inhibition of tumour necrosis factor (TNF-). The mechanisms that underlie the properties of thalidomide are still unclear in interstitial lung disease.

We investigated the potential inhibitory effects of thalidomide at concentrations of 0.1 mM, 0.01 mM and 0.001 mM on the production of transforming growth factor-, TNF-, IL-1, IL-6, IL-8, IL-10, IL-12p70, IL-12p40 and IL-18 by alveolar macrophages from bronchoalveolar lavage in 8 patients with sarcoidosis, 8 with hypersensitivity pneumonitis (HP) and 12 with idiopathic pulmonary fibrosis (IPF).

In sarcoidosis and HP patients, thalidomide induced a dose-dependent suppression of lipopolysacchride (LPS) stimulated TNF-, IL-12p40 and IL-18 release (p<0.05 or p<0.01). At the highest thalidomide concentration (0.1 mM), the LPS stimulated IL-8 production was also decreased (p<0.05). In IPF patients, although the spontaneous production of TNF-, IL-12p40, IL-18 and IL-8 was lower than in sarcoidosis and HP patients, with LPS stimulation the cytokines were significantly elevated and also inhibited by thalidomide.

Thalidomide may be a potential drug to improve the therapeutic regimens for sarcoidosis, HP and IPF through reducing TNF-, IL-12p40, IL-18 and IL-8 production.

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