IL18BP

IL18BP Full Name

interleukin 18 binding protein

IL18BP Introduction

Interleukin-18 binding protein (IL-18BP) is a naturally occurring, secreted glycoprotein that functions as a high-affinity endogenous inhibitor of the pro-inflammatory cytokine interleukin-18 (IL-18). In humans, the IL18BP gene is located on chromosome 11q13.4 and encodes multiple isoforms through alternative splicing, with IL-18BP isoform a being the most abundant and well-characterized. Structurally, IL-18BP contains a single immunoglobulin-like domain and lacks a transmembrane domain, enabling it to circulate freely and interact directly with IL-18 in extracellular spaces. It is constitutively expressed by various cell types, including immune and epithelial cells, and its expression can be strongly induced by interferon-γ (IFN-γ).

Figure 1.The structural basis for receptor recognition of human interleukin-18.(Source: Tsutsumi N.2014)

Functional Role and Mechanism of Action
The primary function of IL-18BP is to regulate IL-18 activity by acting as a soluble decoy receptor. It binds to IL-18 with extremely high affinity (in the picomolar range), preventing IL-18 from engaging its functional heterodimeric receptor complex composed of IL-18Rα and IL-18Rβ. By sequestering free IL-18, IL-18BP effectively blocks downstream signaling pathways—particularly the activation of NF-κB and the induction of IFN-γ—that drive inflammatory and Th1-type immune responses. This regulatory role is essential for maintaining immune homeostasis, preventing excessive inflammation, and limiting tissue damage under physiological and stress conditions.

Pathophysiological Role in Disease
Dysregulation of the IL-18/IL-18BP axis is central to several severe inflammatory and autoimmune conditions. Elevated levels of free IL-18, often due to a relative deficiency of IL-18BP, are a hallmark of macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH), driving life-threatening cytokine storms. It is also implicated in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). Conversely, certain viruses, such as poxviruses, encode viral homologs of IL-18BP to evade host immunity, underscoring its critical role in infectious disease.

Alternate Names for IL18BP

IL18BP; interleukin 18 binding protein; IL18BPa; interleukin-18-binding protein; IL-18BP; tadekinig-alfa; MC51L-53L-54L homolog gene product;

• 1.Tsutsumi N, Kimura T, Arita K, et al. The structural basis for receptor recognition of human interleukin-18. Nature communications, 2014, 5(1): 5340.