GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AS A CAUSE OF PARANEOPLASTIC LEUKEMOID REACTION IN ADVANCED TRANSITIONAL-CELL CARCINOMA

Increasing evidence suggests that paraneoplastic syndromes may be medi ated by tumour-related cytokine release, although the specific factor( s) involved remain poorly defined. Colony-stimulating factors (CSF) an d interleukins (IL) promote colony growth in semi-solid media and, whe n administered in recombinant form, increase blood counts in patients. However, normal serum CSF levels in individuals with physiologic bloo d counts and the relationship between specific serum CSF levels and pa raneoplastic leukaemoid reaction are not well established. In this stu dy, we found that normal serum levels of granulocyte-macrophage CSF (G M-CSF), as measured by ELISA, were generally < 55 pg ml-1, IL-3, < 30 pg ml-1; and granulocyte CSF (GM-CSF), < 50 pg ml-1. In contrast, high levels of GM-CSF (132 pg ml-1), but not G-CSF or IL-3, were found in a patient with a transitional cell carcinoma of the renal pelvis and i ncreased leukocytosis correlating with the tumour burden. The GM-CSF w as biologically active, as demonstrated by its ability to stimulate co lony growth in vitro. Based on these results it appears that autonomou s production of GM-CSF is one possible pathophysiologic mechanism unde rlying leukaemoid reaction in cancer patients.