Production of interleukin‐1β and interleukin‐6 in hepatoblastoma

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Abstract
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 I4 untreated patients with hepatoblastoma for this cytokine and in addition for interleukin‐I α (IL‐Iα), interleukin‐Iβ (IL‐Iβ) and tumor necrosis factor‐α (TNF‐α), all of which are known to induce IL‐6 production. High serum levels of IL‐6 were only found in 3/I4 patients; the other cytokines were not detectable. In contrast, I2/I4 tumors produced substantial amounts of IL‐6 in primary cell culture, while IL‐Iβ was found in 3/I4 supernatants; IL‐Iα and TNF‐α 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‐Iβ, but neither IL‐Iα, TNF‐α 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‐I 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‐Iβ and supposedly some other, as yet unidentified, mediator.