Recombinant Human IL-18 protein

Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the interleukin-1 (IL-1) family, was initially identified as an interferon-gamma (IFN-γ)-inducing factor. It is synthesized as an inactive 24 kDa precursor (pro-IL-18) primarily by macrophages, dendritic cells, and epithelial cells, requiring proteolytic cleavage by caspase-1 or other proteases (e.g., caspase-4/5/11) to release its bioactive 18 kDa mature form. Structurally, IL-18 shares homology with IL-1β, adopting a β-trefoil fold that binds to its heterodimeric receptor complex, IL-18Rα and IL-18Rβ, activating downstream NF-κB and MAPK signaling pathways.

Functionally, IL-18 drives Th1-type immune responses by synergizing with IL-12 to enhance IFN-γ production in T cells and natural killer (NK) cells. However, its role extends beyond inflammation: in the absence of IL-12. IL-18 can promote Th2 responses, regulatory T cell activity, or even paradoxical immunosuppressive effects depending on the microenvironment. This duality underscores its involvement in diverse pathologies, including autoimmune diseases, metabolic disorders, and cancer, where it may either exacerbate inflammation or support immune evasion.

Recombinant IL-18 protein, produced via bacterial (e.g., *E. coli*) or mammalian expression systems, enables mechanistic studies and therapeutic exploration. Bacterial systems yield non-glycosylated but bioactive protein, while mammalian systems (e.g., HEK293 cells) generate glycosylated forms closer to native human IL-18. High-purity recombinant IL-18 is critical for *in vitro* assays (e.g., lymphocyte activation) and *in vivo* models to dissect its immunoregulatory networks. Clinically, recombinant IL-18 has been explored in cancer immunotherapy to boost NK/T cell cytotoxicity, though challenges persist due to its context-dependent effects and potential toxicity. Conversely, IL-18-binding protein (IL-18BP), a natural antagonist, is being investigated to counteract excessive IL-18 in inflammatory diseases. Ongoing research aims to harness IL-18's pleiotropic biology for targeted therapies while mitigating adverse outcomes.