Am. J. Respir. Crit. Care Med., Volume 159, Number 2, February 1999, 508-511

Pentoxifylline Inhibits TNF- Production from Human Alveolar Macrophages

LEILA JOHN MARQUES, LING ZHENG, NIKOLAOS POULAKIS, JOSUNE GUZMAN, and ULRICH COSTABEL

Department of Pneumology and Allergy, Ruhrlandklinik, Medical Faculty, University of Essen, Essen, Germany; and General and Experimental Pathology, Ruhr University, Bochum, Germany

Tumor necrosis factor- (TNF-) is an important proinflammatory cytokine. Recently, pentoxifylline (POF) has been shown to suppress the synthesis of TNF- from lipopolysaccharide (LPS)-stimulated human monocytes in cell cultures and in vivo. The aim of this study was to investigate whether POF-induced suppression of TNF- secretion affects peripheral blood monocytes (PBM) and alveolar macrophages (AM) equally, and whether POF is able to suppress the spontaneous TNF- production from AM in pulmonary sarcoidosis in vitro. In seven patients without interstitial lung disease we studied the effect of POF on LPS-stimulated PBM and AM cultured for 24 h. In six patients with sarcoidosis we investigated the effect of POF on the enhanced spontaneous TNF- production by AM in vitro. POF induced a dose-dependent suppression of the LPS-stimulated TNF- production which was not different for PBM and AM, respectively. In sarcoidosis, POF inhibited the spontaneous TNF- production of AM at 0.1 mM by 91% and at 1 mM by 98%. In conclusion, POF inhibits LPS-induced TNF- production from PBM and AM to a similar extent and can also inhibit the exaggerated spontaneous TNF- production from AM in sarcoidosis in vitro. This may be the basis for further clinical trials to evaluate POF as an immunotherapeutic agent in sarcoidosis.

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