Clinical use of GM-CSF in the prevention of liver metastases; A pilot study in the rat on the effect of rmGM-CSF on Kupffer cells

The present study describes the effect of recombinant murine Granulocyte Ma crophage-Colony Stimulating Factor (rmGM-CSF) pre-treatment of male WAG/Rij rats on the number of KCs in the liver, KC mediated cytotoxicity ex-vivo" and the effect on experimentally induced" minimal residual disease (MRD) in the liver. Our results show that: 1) the mean KC yield per gram liver increased from 1 .5 +/- 0.2 to 2.2 +/- 0.2 (p < 0.05, Mann-Whitney test) after rmGM-CSF trea tment, 2) the mean percentage of KC mediated cytotoxicity against CC531 inc reased from 20.0 +/- 0.5 to 42.0 +/- 1.0 after rmGM-CSF treatment (p < 0.05 ), and 3) the outgrowth of small tumour foci after inoculation of 1 x 10(5) CC531 tumour cells in the portal vein was prevented in the pre-treatment g roup. At tumour loads of 1 x 10(6) and 0.5 x 10(6) CC531 tumour cells, howe ver, no prophylactic effect of rmGM-CSF was found. In conclusion, our data demonstrate increased numbers of isolated KCs with enhanced cytotoxic capacity after pre-treatment with rmGM-CSF and in vivo r eduction of MRD. These results indicate that peri-operative immunomodulatio n with GM-CSF may be of clinical use as an adjuvant strategy in patients wi th colorectal carcinoma, who are at risk of developing hepatic metastases.