Production of interleukin-1 beta and interleukin-6 in hepatoblastoma.
Thrombocytosis and fever are frequent symptoms in children with hepatoblastoma. Interleukin-6 (IL-6) has been shown to mediate thrombocytosis and an acute-phase reaction including fever. We therefore investigated samples from 14 untreated patients with hepatoblastoma for this cytokine and in addition for interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), all of which are known to induce IL-6 production. High serum levels of IL-6 were only found in 3/14 patients; the other cytokines were not detectable. In contrast, 12/14 tumors produced substantial amounts of IL-6 in primary cell culture, while IL-1 beta was found in 3/14 supernatants; IL-1 alpha and TNF-alpha were always negative. Immunoenzymatic staining of fresh tumors revealed that IL-6 is not produced by the tumor cells, but rather by surrounding fibroblasts and endothelial cells. In tumor cells only IL-1 beta, but neither IL-1 alpha, TNF-alpha nor IL-6, could be detected. In co-culture experiments with fibroblasts and endothelial cells, addition of hepatoblastoma cells enhanced IL-6 production. Including an IL-1 receptor antagonist abolished this effect incompletely. Our results suggest that tumor cells in hepatoblastoma induce IL-6 production in surrounding fibroblasts and endothelial cells by virtue of their endogenous secretion of IL-1 beta and supposedly some other, as yet unidentified, mediator.
Department of Pediatric Surgery, Medical School of Hanover, Germany.
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D
von Schweinitz
M R
MR
Hadam
K
K
Welte
H
H
Mildenberger
T
T
Pietsch
D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha