Immune-stimulating effects of low-dose perioperative recombinant granulocyte-macrophage colony-stimulating factor in patients operated on for primary colorectal carcinoma.
BACKGROUND
Surgery induces a postoperative immunosuppression, thereby possibly facilitating the outgrowth of pre-existing occult metastases or the seeding of disseminated tumour cells in patients with primary colorectal carcinoma operated on with curative intent. The hypothesis that adjuvant therapy with perioperative recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) would minimize postoperative immunosuppression was investigated in this pilot study.


METHODS
Patients were allocated randomly to receive daily subcutaneous injections with either saline (n = 8) or rhGM-CSF 2.8 microg per kg body-weight (n = 8) from 3 days before operation until 4 days afterwards. Phytohaemagglutinin (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 levels 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 while enhancing the expression of HLA-DR in the postoperative period. Additionally, both postoperative plasma IL-6 levels and the incidence of fever tended to be higher in the rhGM-CSF group.


CONCLUSIONS
In this pilot study, perioperative administration of low-dose rhGM-CSF stimulated certain immune functions that are normally depressed after operation. The implications for the antitumour responses directly after operation and the formation of liver metastases are currently under investigation.
Mels
A K
AK
Department of Surgery, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands.
Statius Muller
M G
MG
van Leeuwen
P A
PA
von Blomberg
B M
BM
Scheper
R J
RJ
Cuesta
M A
MA
Beelen
R H
RH
Meijer
S
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001831:Body Temperature / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000097:blood; D007430:Intraoperative Care / Q000379:methods; D007964:Leukocytosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010835:Phytohemagglutinins / Q000032:analysis; D010865:Pilot Projects; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D006684:HLA-DR Antigens; D015850:Interleukin-6; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor