Pentoxifylline at clinically achievable levels inhibits FMLP-induced neutrophil responses, but not priming, upregulation of cell-adhesion molecules, or migration induced by GM-CSF.

Pentoxifylline (PTX) administered after bone-marrow transplantation reduces procedure-related organ damage mediated by TNF alpha. GM-CSF is also given post-transplant to stimulate earlier neutrophil recovery. Because PTX has been shown to inhibit neutrophil function, we sought to determine whether it also inhibited the effects of GM-CSF on neutrophil activity. The study confirmed that PTX at clinically achievable concentration (5-10 mumol/l) attenuated the responses of human neutrophils to chemotactic peptide, whereas it did not inhibit the effect of GM-CSF on neutrophil function even at high concentrations. In experiments with human neutrophils, neither the direct effects of GM-CSF such as stimulation of migration and increased expression of CD11b, nor the priming effects of GM-CSF on the respiratory burst, were inhibited by PTX. In experiments with monkeys, intravenous administration of PTX did not block subsequent GM-CSF-induced neutrophil CD11b upregulation or phagocyte margination, even when near millimolar plasma levels of pentoxifylline were obtained. The retention of cytokine-stimulated activities suggests that PTX will not compromise the response of neutrophils to stimuli from infectious foci.