Autoregulation of the interleukin-1 system and cytokine-cytokine interactions in primary human astrocytoma cells

Cytokines are proposed to play important roles in brain tumor biology. Previous studies reported on interleukin-1 beta (IL-1 beta) production and IL-1 receptor type I (IL-1RI, signaling receptor) expression in human astrocytomas, and on IL-1 beta action in astrocytoma cell lines. However, all studies that have tested the direct action of cytokines have used exclusively astrocytoma cell lines, which do not recapitulate the in situ astrocytoma. Here, we demonstrate that astrocytoma cells obtained shortly after tumor neurosurgical resection respond to the direct application of human IL-1 beta with a significant upregulation of IL-1 alpha, IL-1 beta, IL-1RI, and tumor necrosis factor-alpha (TNF-alpha) mRNAs, IL-1 receptor antagonist (IL-1R alpha, an endogenous inhibitor that blocks IL-1 alpha and IL-1 beta actions) mRNA was not upregulated. Application of heat-inactivated IL-1 beta had no effect on any cytokine component examined, demonstrating specificity of action. On the other hand, IL-1 beta application did not modulate any cytokine component in acutely resected and dissociated primitive neuroectodermal tumor cells. The data have implications for a positive autoregulatory IL-1 beta feedback system and synergistic IL-1 beta <-> TNF-alpha interactions, which can be involved in the growth of pilocytic astrocytomas. The results together with our previous studies also support the notion that IL-1R alpha or a compound with similar cytokine inhibitory activity could be useful for brain immunotherapy of astrocytomas. (C) 2000 Elsevier Science Inc.