Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages

Am J Respir Crit Care Med. 1999 Feb;159(2):508-11. doi: 10.1164/ajrccm.159.2.9804085.


Tumor necrosis factor-alpha (TNF-alpha) is an important proinflammatory cytokine. Recently, pentoxifylline (POF) has been shown to suppress the synthesis of TNF-alpha 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-alpha secretion affects peripheral blood monocytes (PBM) and alveolar macrophages (AM) equally, and whether POF is able to suppress the spontaneous TNF-alpha 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-alpha production by AM in vitro. POF induced a dose-dependent suppression of the LPS-stimulated TNF-alpha production which was not different for PBM and AM, respectively. In sarcoidosis, POF inhibited the spontaneous TNF-alpha production of AM at 0.1 mM by 91% and at 1 mM by 98%. In conclusion, POF inhibits LPS-induced TNF-alpha production from PBM and AM to a similar extent and can also inhibit the exaggerated spontaneous TNF-alpha 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lipopolysaccharides / pharmacology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism*
  • Macrophages, Alveolar / pathology
  • Male
  • Middle Aged
  • Pentoxifylline / pharmacology*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Sarcoidosis, Pulmonary / drug therapy
  • Sarcoidosis, Pulmonary / metabolism
  • Sarcoidosis, Pulmonary / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Biomarkers
  • Lipopolysaccharides
  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Pentoxifylline