The differential effect of pentoxifylline on cytokine production by alveolar macrophages and its clinical implications

Respir Med. 1999 Jan;93(1):52-7. doi: 10.1016/s0954-6111(99)90077-x.

Abstract

The aim of this study was to investigate the effects of pentoxifylline (PTX) on the production of TNF-alpha, IL-1 beta, IL-6 and GM-CSF by lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM). AM and peripheral blood monocytes (PBM) from 10 patients were cultured for 24 h in the presence of LPS (10 micrograms ml-1) and PTX at concentrations of 2.0 mM, 1.0 mM, 0.5 mM, 0.1 mM and 0.01 mM. TNF-alpha and GM-CSF were measured from the culture supernatants of both the AM and PBM from all 10 patients and IL-1 beta and IL-6 from the culture supernatants of the AM from five patients. The TNF-alpha production by AM was significantly suppressed in the presence of PTX at concentrations of 2.0 and 1.0 mM, while production of IL-1 beta, IL-6 and GM-CSF remained unaffected. In PBM cultures, PTX significantly suppressed the production of TNF-alpha and GM-CSF, at all tested concentrations. The present study provides evidence that PTX selectively suppresses the production of TNF-alpha by LPS-stimulated AM and may have a role in the treatment of lung diseases where TNF-alpha is involved. The mode of administration of PTX should take into account the suppressive effect of this drug on GM-CSF production by PBM.

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Depression, Chemical
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Leukocytes, Mononuclear / drug effects
  • Lipopolysaccharides / pharmacology
  • Lung Diseases / immunology
  • Macrophage Activation
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / immunology*
  • Male
  • Middle Aged
  • Pentoxifylline / pharmacology*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Pentoxifylline