INDUCTION OF IL-1 - INDEPENDENT PRODUCTION OF IL-1-ALPHA AND IL-1-BETA

Lipopolysaccharide (LPS) either in its soluble form or associated with multilamellar phospholipid vesicles (liposomes) was investigated for its ability to induce human monocyte interleukin (IL)-1α and IL-1β. When human monocytes were activated in vitro by LPS either in its soluble form or presented at the surface of lyophilized multilamellar vesicles (Lyo-MLV-LPS), both IL-1α and IL-1β were detected intracellularly and extracellularly, using specific antisera. In correlation with these findings, the mRNAs for IL-1α and IL-1β were both found by Northern blot analysis. However, when human monocytes were stimulated by LPS incorporated into multilamellar vesicles which had not been previously lyophilized, a different pattern of IL-1 protein and message was observed. IL-1α activity was detected only intracellularly and not in the supernatant, while IL-1β was not produced at all. Northern blotting revealed only mRNA for IL-1α as soon as 0.5 h after stimulation and none for IL-1β. These data indicate independent induction of IL-1α and IL-1β. Moreover, it appears that the regulation occurs at the transcriptional level, since with MLV-LPS only the mRNA for IL-1α was induced. The lack of IL-1β could be due to either a blockage at the DNA level, an undetectable level of IL-1β mRNA, or a very short halflife for IL-1β mRNA. These findings indicate that although IL-1α and IL-1β may have identical biological properties and share the same receptor, their induction and secretion are regulated by independent pathways. Moreover, the same activator, presented in a different manner to the same cells can induce different consequences. © 1992.