title: The differential effect of pentoxifylline on cytokine production by alveolar macrophages and its clinical implications.
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.
authors.affiliation: Fourth Department of Pulmonary Medicine, Athens Chest Disease Hospital Sotiria, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Poulakis
authors.forename: G
authors.initials: G
authors.lastname: Androutsos
authors.forename: D
authors.initials: D
authors.lastname: Kazi
authors.forename: A
authors.initials: A
authors.lastname: Bastas
authors.forename: A
authors.initials: A
authors.lastname: Provata
authors.forename: C
authors.initials: C
authors.lastname: Bitsakou
authors.forename: T
authors.initials: T
authors.lastname: Kontozoglou
authors.forename: C
authors.initials: C
authors.lastname: Polyzogopoulou
authors.forename: A
authors.initials: A
authors.lastname: Tassiopoulou
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003864:Depression, Chemical; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008171:Lung Diseases / Q000276:immunology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010431:Pentoxifylline