Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions

Thomas Hartung, Wolf Dietrich Doecke, Daniela Bundschuh, Mary Ann Foote, Florian Gantner, Corinna Hermann, Andre Lenz, Steven Milwee, Bill Rich, Bernadett Simon, Hans Dieter Volk, Sonja Von Aulock, Albrecht Wendel

Research output: Contribution to journalArticle

Abstract

Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 μg filgrastim (recombinant methionyl human granulocyte colony- stimulating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and interferon gamma (IFN-γ) release by whole blood in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added in vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-γ and TNF-α release, suggesting that the anti- inflammatory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphocyte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgrastim induced doubling of all T-cell populations by day 8. Filgrastim decreased proinflammatory cytokine production and lymphocyte proliferation ex vivo throughout prolonged treatment at all doses. This indicates that endogenous granulocyte colony-stimulating factor may counterregulate the inflammatory cytokine cascade and implies a potential indication for filgrastim in chronic inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)415-424
Number of pages10
JournalClinical pharmacology and therapeutics
Volume66
Issue number4
DOIs
StatePublished - Nov 1 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Hartung, T., Doecke, W. D., Bundschuh, D., Foote, M. A., Gantner, F., Hermann, C., Lenz, A., Milwee, S., Rich, B., Simon, B., Volk, H. D., Von Aulock, S., & Wendel, A. (1999). Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions. Clinical pharmacology and therapeutics, 66(4), 415-424. https://doi.org/10.1053/cp.1999.v66.a101210