Regulation of human IL-18 mRNA expression.

As virtually nothing is known about the pattern of expression of human IL-18, we investigated certain factors that may contribute to the regulation of IL-18 mRNA accumulation and compared this with regulation of the human gene encoding the p40 chain of IL-12, a cytokine that shares similar biologic activity with IL-18. IL-18 mRNA was expressed constitutively in unstimulated PBMC or monocytes, unlike p40, which required induction by a stimulus. Upon stimulation, IL-18 transcript accumulation was enhanced with an earlier and more transient pattern of expression than IL-12 p40 mRNA. Bacteria-derived stimuli and priming with IFN-gamma or IL-4 also upregulated IL-18 mRNA in a fashion similar to that of IL-12 p40. IL-10 exerted an inhibitory effect on IL-18 mRNA accumulation, though not as markedly as in the suppression of IL-12 p40 by IL-10. Finally, unlike IL-12 p40 mRNA, the constitutive accumulation of IL-18 transcripts by unstimulated cells was amplified in the presence of the translational blocker cycloheximide, which also caused a superinduction of IL-18 expression after Staphylococcus aureus stimulation.