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

The aim of this study was to investigate the effects of pentoxifylline (PTS ) on the production of TNF-alpha IL-1 beta IL-6 and GM-CSF by lipopolysacch aride (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 mu g ml(-1) ) and PTX at concentrations of 2.0 mM, 1.0 mw, 0.5 mM, 0.1 mM and 0.01 mM. TNF-alpha and GM-CSF were measured from the culture supernatants of both th e AM and PBM from all 10 patients and IL-1 beta and IL-6 from the culture s upernatants 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 su ppressed the production of TNF-alpha and GM-CSF, at all tested concentratio ns. The present study provides evidence that PTX selectively suppresses the pro duction of TNF-alpha by LPS-stimulated AM and may have a role in the treatm ent of lung diseases where TNF-alpha is involved. The mode of administratio n of PTX should take into account the suppressive effect of this drug on GM -CSF production by PBM.