Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primarycolorectal carcinoma
Ak. Mels et al., Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primarycolorectal carcinoma, BR J SURG, 88(4), 2001, pp. 539-544
Background: Surgery induces a postoperative immunosuppression, thereby poss
ibly facilitating the outgrowth of pre-existing occult metastases or the se
eding of disseminated tumour cells in patients with primary colorectal carc
inoma operated on with curative intent. The hypothesis that adjuvant therap
y with perioperative recombinant human granulocyte-macrophage colony-stimul
ating factor (rhGM-CSF) would minimize postoperative immunosuppression was
investigated in this pilot study.
Methods: Patients were allocated randomly to receive daily subcutaneous inj
ections with either saline (n = 8) or rhGM-CSF 2.8 mug per kg body-weight (
n = 8) from 3 days before operation until 4 days afterwards. Phytohaemagglu
tinin (PHA) skin test reactivity, monocyte human leucocyte antigen (HLA) DR
expression and the extent of the acute-phase response, by determination of
white blood cell count and differentiation, plasma interleukin (IL) 6 leve
ls and body temperature in the perioperative period, were examined.
Results: rhGM-CSF treatment minimized postoperative suppression in PHA skin
test reactivity and increased the numbers of neutrophils and monocytes whi
le enhancing the expression of HLA-DR in the postoperative period. Addition
ally, both postoperative plasma IL-6 levels and the incidence of fever tend
ed to be higher in the rhGM-CSF group.
Conclusion: in this pilot study, perioperative administration of low-dose r
hGM-CSF stimulated certain immune functions that are normally depressed aft
er operation. The implications for the antitumour responses directly after
operation and the formation of liver metastases are currently under investi
gation.