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Interleukin-18 Binding Protein (IL-18BP) is a naturally occurring inhibitor of the proinflammatory cytokine, Interleukin-18 (IL-18). IL-18 is a cytokine that plays a crucial role in the immune response by inducing the production of interferon-gamma (IFN-γ), which is essential for the activation of macrophages and the promotion of T-helper type 1 (Th1) immune responses . However, excessive IL-18 activity can lead to chronic inflammation and has been implicated in various inflammatory diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis, and psoriasis .
IL-18BP is a soluble protein that binds to IL-18 with high affinity, preventing it from interacting with its receptor on the cell surface . This binding effectively neutralizes IL-18, inhibiting its ability to induce IFN-γ production and subsequent inflammatory responses . The protein is constitutively expressed and secreted by mononuclear cells, and its levels can be elevated in response to inflammatory stimuli .
The production of recombinant human IL-18BP (rhIL-18BP) has been achieved using various expression systems, including eukaryotic animal cells and bacterial systems such as Escherichia coli (E. coli) . The use of E. coli for recombinant protein production offers several advantages, including high yield, cost-effectiveness, and ease of scaling up . In recent studies, novel approaches have been developed to enhance the expression and stability of rhIL-18BP. For example, the fusion of IL-18BP with the small ubiquitin-related modifier (SUMO) tag and the human IgG1 Fc fragment has been shown to improve soluble expression and prolong the protein’s in vivo lifespan .
The anti-inflammatory properties of IL-18BP make it a promising candidate for the treatment of various inflammatory diseases. Preclinical studies have demonstrated the efficacy of rhIL-18BP in inhibiting IL-18-induced IFN-γ production and ameliorating symptoms in animal models of diseases such as ulcerative colitis . The therapeutic potential of IL-18BP is further supported by its ability to modulate the balance between proinflammatory and regulatory cytokines, thereby restoring immune homeostasis .