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Effect of Plasma TNF‐α on Filgrastim‐Stimulated Hematopoiesis in Mice and Humans
Author(s) -
Petros William P.,
Rabinowitz Josh,
Gibbs John P.,
Hall Iris H.,
Stuart Ann R.,
Peters William P.
Publication year - 1998
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1998.tb03902.x
Subject(s) - filgrastim , tumor necrosis factor alpha , haematopoiesis , granulopoiesis , medicine , leukopenia , immunology , chemotherapy , lipopolysaccharide , pharmacology , in vivo , neutropenia , cancer research , oncology , biology , stem cell , genetics , microbiology and biotechnology
Study Objective . To delineate possible explanations for a nonmonotone hematopoiesis, dose‐response curve with filgrastim therapy after high‐dose chemotherapy. Design . Sequential two‐phase study. Settings . University teaching hospital and basic pharmaceutical sciences laboratory. Subjects . Thirty‐nine patients with breast cancer or melanoma and 15 normal CF‐1 male mice. Interventions . Serial blood samples were obtained from patients after high‐dose chemotherapy to evaluate hematopoiesis and tumor necrosis factor‐α (TNF‐α) concentrations. Murine hematopoiesis was induced by filgrastim with or without coadministration of lipopolysaccharide. Measurements and Main Results . Detection of plasma TNF‐α in patients corresponded to substantially slower recovery of granulocytes, erythrocytes, and platelets, and was directly proportional to the prescribed dosage of filgrastim. Lipopolysaccharide stimulated the secretion of TNF‐α in mice and totally aberrated filgrastim‐induced granulopoiesis. Conclusions . This in vivo evidence suggests that regulatory pathways involving endogenous cytokines may override the effect of recombinant cytokines.