Interleukin-6 messenger RNA (IL-6 mRNA) (IL-6 mRNA)

Interleukin-6 (IL-6) messenger RNA (mRNA) is the nucleic acid template responsible for the synthesis of the IL-6 protein, a pleiotropic cytokine that mediates critical aspects of the immune response, inflammation, and hematopoiesis (NCBI Gene ID: 3569). The stability and translation of IL-6 mRNA are tightly controlled by various RNA-binding proteins and endoribonucleases, such as Regnase-1, which prevent excessive inflammatory signaling under normal conditions (PMID: 29103911). Pathological overexpression of IL-6 mRNA is a hallmark of several chronic inflammatory diseases, including rheumatoid arthritis, Castleman disease, and systemic juvenile idiopathic arthritis, where it drives the cytokine storm and systemic inflammation (PMID: 31108135). While traditional therapies target the IL-6 protein or its receptor (IL-6R), targeting the mRNA itself using antisense oligonucleotides (ASOs) or RNA interference (RNAi) offers a strategy to inhibit the production of the cytokine at its source. For instance, the investigational drug IONIS-IL6-LRx (ION-606) is an antisense oligonucleotide designed to bind to IL-6 mRNA and trigger its degradation via RNase H1, thereby reducing systemic IL-6 levels (Ionis Pharmaceuticals). This approach may provide more durable suppression of IL-6 signaling compared to protein-targeting antibodies and is being explored for conditions like chronic kidney disease and other inflammatory disorders (ClinicalTrials.gov NCT04039386).

Other names

IL6 mRNAB-cell stimulatory factor 2 mRNAInterferon beta-2 mRNAHepatocyte stimulatory factor mRNABSF2 mRNAIFNB2 mRNA

Antisense oligonucleotide-mediated RNase H1 cleavage of the target mRNA, preventing translation into the Interleukin-6 protein.