INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION INDUCED BY INTERLEUKIN (IL)-1-BETA OR AN IL-1-BETA FRAGMENT IS BLOCKED BY AN IL-1 RECEPTOR ANTAGONIST AND A SOLUBLE IL-1 RECEPTOR

The effects of a recombinant human interleukin-1 (IL-1) receptor antagonist (IL-Ira) and a recombinant human soluble IL-1 receptor (sIL-1R) on cytokine-induced intercellular adhesion molecule-1 (ICAM-1) expression in a human glioblastoma cell line and a neuroblastoma cell line were determined. Cells were incubated with IL-1beta, tumor necrosis factor (TNF)alpha and interferon (IFN)gamma. Cells were also tested under identical conditions with an IL-1beta synthetic peptide fragment (IL-1beta208-240) previously shown to possess biological activity. IL-1beta, TNFalpha and IFNgamma potentiated ICAM-1 expression in both cell lines in a dose-related manner. The IL-1beta208-240 fragments, corresponding to the rabbit, rat and human sequences, enhanced ICAM-1 expression in glioblastoma cells at high doses. ICAM-1 expression induced by IL-1beta, rabbit IL-1beta208-240 and human IL-1beta208-240 was blocked by the IL-1ra, while TNFalpha- and IFNgamma-induced ICAM-1 expression were not. ICAM-1 expression induced by IL-1beta and human IL-1beta208-240 was also blocked by the sIL-1R. Our findings suggest that IL1beta208-240 acts as an IL-1beta agonist in enhancing ICAM-1 expression in vitro and that this effect is receptor-mediated