INTERLEUKIN-6 PRODUCTION AND SECRETION IN HUMAN-MELANOMA CELL-LINES -REGULATION BY INTERLEUKIN-1

These investigations were designed to test the hypothesis that exogeno us and/or endogenous interleukin-1 (IL-1) regulates interleukin-6 (IL- 6) production in human melanoma cell lines, Ten cell lines were examin ed 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 line s also produced intracellular and secreted IL-6 as evidenced by positi ve reaction for IL-6 using immunohistochemistry staining and ELISA met hods; three others produced only intracellular IL-6. Addition of exoge nous IL-1 alpha was shown to have the following effects on IL-6 produc tion: first, de novo induction of detectable IL-6 intracellular protei n and secreted IL-6 in a cell line void of either; second, stimulation of IL-6 secretion in all three cell lines producing only intracellula r 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. Experime nts employing the IL-1 receptor antagonist confirmed an extracellular receptor-mediated role of IL-1 in regulation of IL-6 production in suc h cells. These results indicate that IL-1 can regulate IL-6 in human m elanoma cells; however, heterogeneity in the constitutive expression a s well as variability in response exists with respect to these two cyt okines.