白血球機能制御による新たなる抗炎症治療戦略：Granulocyte colony-stimulating factor (G-CSF)療法

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycosylated protein that was originally identified as a granulopoietic growth factor. It has been shown that G-CSF stimulates the proliferation and maturation of neutrophil precursor cells as well as increases such neutrophil functions as chemotaxis, phagocytosis, and bactericidal activity. G-CSF has drawn recent attention as a therapeutic drug for sepsis, because studies show that G-CSF not only selectively stimulates the proliferation of neutrophils but also plays an important role as a multipotent modulator of acute inflammation.We previously reported an increased serum G-CSF concentration concomitant with an elevated absolute neutrophil count showing a left shift toward more immature forms, and that neutrophil phagocytic and bactericidal activity is maintained in patients with trauma or sepsis. We suggested that G-CSF plays an important role in neutrophil maturation and the maintenance of neutrophil function in inflammatory response associated with trauma and sepsis.We also investigated the clinical effects of recombinant human G-CSF (rhG-CSF) administration in patients with sepsis who lack appropriate neutrophilia. We concluded that rhG-CSF administration attenuates inflammatory responses without inducing tissue injury. In addition, we found the difference in responses after rhG-CSF in each patients with sepsis. In the good response group, rhG-CSF administration markedly improved the severity of illness and produced a good outcome. The endogenous G-CSF level in blood showed lower than that in the poor response patients before rhG-CSF administration. Immature neutrophils was significantly higher in poor response group than those in good response group. Those results suggest that rhG-CSF was effective in septic patients with a low percentage of immature neutrophils and insufficient endogenous G-CSF.Some recent reports, however, have suggested that rhG-CSF treatment in patients receiving cytotoxins can be associated with pulmonary toxicity. However, we revealed that rhG-CSF causes leukocyte stiffness but attenuates inflammatory response without inducing lung injury in septic patients.This review will provide an overview of our current understanding of the role of G-CSF as an anti-inflammatory modulator in patients with sepsis.