How to leverage an endogenous immune defense mechanism: the example of granulocyte colony-stimulating factor.
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.
Hartung
Thomas
T
Biochemical Pharmacology, University of Konstanz, Konstanz, Germany.
Von Aulock
Sonja
S
Schneider
Christian
C
Faist
Eugen
E
D000368:Aged; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D018805:Sepsis / Q000276:immunology* / Q000517:prevention & control*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim