Granulocytosis and thrombocytosis in renal cell carcinoma: a pro-inflammatory cytokine response originating in the tumour.
BACKGROUND
In up to 20% of patients with renal cell cancer (RCC) an inflammatory response consisting of low-grade fever, weight loss and an elevated ESR and CRP may occur with modest granulocytosis and thrombocytosis. Clinical and experimental data suggest a pathogenic role for tumour-derived cytokine production, especially interleukin-6.


METHODS
A 79-year-old female with RCC presented with low-grade fever, weight loss and overt granulocytosis and thrombocytosis. Radiological examination revealed a right-sided renal tumour. During nephrectomy a gradient between the IL-6 levels in the renal artery and vein was demonstrated, providing direct evidence for in vivo production of IL-6 by the tumour affected kidney, which was confirmed by the demonstration of IL -6 in the tumour cells by immunohistochemical staining and in the supernatant of the homogenised tumour. Cytogenetic examination revealed complex abnormalities including a gain of chromosome 7. In addition we demonstrated production of IL-1alpha, IL-1beta, IL-8 and ICAM-1 in the tumour with systemic elevated levels of IL-6 and IL-8 with secondary increased serum G-CSF and TPO levels.


CONCLUSIONS
We have provided direct evidence for the production of pro-inflammatory cytokines by renal cancer cells in a patient with RCC and a profound inflammatory response, with a central role of IL-6, probably due to a gain of chromosome 7. The extreme granulocytosis and thrombocytosis may have resulted from the secondary systemic production of G-CSF and TPO.
van Rossum
A P
AP
Laboratory for Clinical Chemistry and Haematology, Bronovo Hospital, the Hague, the Netherlands.
Vlasveld
L Th
LT
Vlasveld
I N
IN
Jansen
P M
PM
Dik
W A
WA
Hooijkaas
H
H
Castel
A
A
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000276:immunology* / Q000601:surgery; D016207:Cytokines / Q000276:immunology*; D017809:Fatal Outcome; D005260:Female; D006098:Granulocytes; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007378:Interleukins / Q000032:analysis*; D007680:Kidney Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000276:immunology* / Q000601:surgery; D007964:Leukocytosis / Q000150:complications / Q000276:immunology*; D011859:Radiography; D013922:Thrombocytosis / Q000150:complications / Q000276:immunology*
D016207:Cytokines; D007378:Interleukins