How to leverage an endogenous immune defense mechanism: The example of granulocyte colony-stimulating factor

Thomas Hartung, Sonja Von Aulock, Christian Schneider, Eugen Faist

Research output: Contribution to journalReview articlepeer-review

Abstract

Our understanding of host defense has exploded during the past two decades. It is temping to take advantage of this knowledge by considering the modulation and control of these mechanisms as therapeutic options. In intensive care medicine, the aim is usually to block an overwhelming inflammatory response, which represents the "bad" side of the double-edged sword of host defense. The obvious danger of such treatment strategies is that impairing the inflammatory reaction means impairing host defense in patients exposed to infectious agents. The alternative approach, i.e., strengthening or supplementing favorable host defense mechanism, has so far been little explored clinically. Granulocyte colony-stimulating factor, the granulocyte colony-stimulating factor, combines the unique properties of an anti-infectious and an anti-inflammatory factor. This attractive profile has led us to various approaches to exploit these immunomodulatory activities. In a recently terminated, placebo-controlled, randomized study, we investigated if prophylactic treatment with rh granulocyte colony-stimulating factor (Filgrastim), at the time a risk can be anticipated such as before an operation, may offer protection from immunoinflammatory dyshomeostasis and thus lower the incidence of postoperative sepsis. Perioperative rh granulocyte colony-stimulating factor administration, compared with placebo treatment, resulted in the prevention of postoperative monocyte deactivation, conservation of an adequate TH1/TH2 ratio, as well as a considerable alleviation of the acute phase response. In parallel, there was a clear tendency toward lowering the rate of postoperative septic complications under the administration of Filgrastim.

Original languageEnglish (US)
Pages (from-to)S65-S75
JournalCritical care medicine
Volume31
Issue number1 SUPPL.
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Clinical trials
  • Endogenous production
  • Granulocyte colony-stimulating factor
  • Infection
  • Inflammation
  • Perioperative immunomodulation
  • Pleiotropy
  • Redundancy
  • Safety
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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