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-α, IL-1β, 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 μg ml −1) and PTX at concentrations of 2·0 m m, 1·0 m m, 0·5 m m, 0·1 m m and 0·01 m m. TNF-α and GM-CSF were measured from the culture supernatants of both the AM and PBM from all 10 patients and IL-1β and IL-6 from the culture supernatants of the AM from five patients. The TNF-α production by AM was significantly suppressed in the presence of PTX at concentrations of 2·0 and 1·0 m m, while production of IL-1β, IL-6 and GM-CSF remained unaffected. In PBM cultures, PTX significantly suppressed the production of TNF-α and GM-CSF, at all tested concentrations. The present study provides evidence that PTX selectively suppresses the production of TNF-α by LPS-stimulated AM and may have a role in the treatment of lung diseases where TNF-α is involved. The mode of administration of PTX should take into account the suppressive effect of this drug on GM-CSF production by PBM.