Effect of plasma TNF-α on filgrastim-stimulated hematopoiesis in mice and humans

William P. Petros, Josh Rabinowitz, John P. Gibbs, Iris H. Hall, Ann R. Stuart, William P. Peters

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)816-823
Number of pages8
JournalPharmacotherapy
Volume18
Issue number4
StatePublished - Jul 1 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

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