Interleukin-6 production and secretion in human melanoma cell lines: regulation by interleukin-1

These investigations were designed to test the hypothesis that exogenous and/or endogenous interleukin-1 (IL-1) regulates interleukin-6 (IL-6) production in human melanoma cell lines. Ten cell lines were examined for IL-1 and IL-6 expression. Six of these 10 lines constitutively expressed detectable IL-6 mRNA by RT-PCR; three of these six cell lines also produced intracellular and secreted IL-6 as evidenced by positive reaction for IL-6 using immunohistochemistry staining and ELISA methods; three others produced only intracellular IL-6. Addition of exogenous IL-1 alpha was shown to have the following effects on IL-6 production: first, de novo induction of detectable IL-6 intracellular protein and secreted IL-6 in a cell line void of either; second, stimulation of IL-6 secretion in all three cell lines producing only intracellular IL-6 protein; and third, quantitative enhancement of IL-6 secretion in cell lines that constitutively secreted IL-6. Three of the 10 lines which secreted IL-6 also constitutively secreted IL-1 alpha. Experiments employing the IL-1 receptor antagonist confirmed an extracellular receptor-mediated role of IL-1 in regulation of IL-6 production in such cells. These results indicate that IL-1 can regulate IL-6 in human melanoma cells; however, heterogeneity in the constitutive expression as well as variability in response exists with respect to these two cytokines.