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Pentoxifylline at clinically achievable levels inhibits FMLP‐induced neutrophil responses, but not priming, upregulation of cell‐adhesion molecules, or migration induced by GM‐CSF
Author(s) -
Roberts Pamela J.,
Yong Kwee L.,
Khwaja Asim,
Johnson Beryl V.,
Pizzey Arnold R.,
Carver Julia E.,
Addison Ian E.,
Linch David C.
Publication year - 1993
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1993.tb00066.x
Subject(s) - pentoxifylline , respiratory burst , granulocyte , integrin alpha m , chemotaxis , immunology , neutrophile , downregulation and upregulation , stimulation , cytokine , medicine , phagocyte , priming (agriculture) , neutrophil extracellular traps , cell adhesion molecule , inflammation , immune system , pharmacology , endocrinology , biology , receptor , biochemistry , botany , germination , gene
Pentoxifylline (PTX) administered after bone‐marrow transplantation reduces procedure‐related organ damage mediated by TNFα. 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 μmol/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.