@Article{ecn.2026.083788,
AUTHOR = {Simone Negrini, Stefania Nicola, Iuliana Badiu, Anna Quinternetto, Ilaria Vitali, Luca Lo Sardo, Luisa Brussino},
TITLE = {The interleukin-18/Interleukin-18 binding protein axis across allergy, systemic autoimmunity, and hyperinflammation: from total to free IL-18},
JOURNAL = {European Cytokine Network},
VOLUME = {37},
YEAR = {2026},
NUMBER = {3},
PAGES = {151--168},
URL = {http://www.techscience.com/ECN/v37n3/69032},
ISSN = {1952-4005},
ABSTRACT = {Interleukin-18 (IL-18) is a pleiotropic IL-1-family cytokine whose clinical relevance depends strongly on context. A central reason is that IL-18 activity is constrained by interleukin-18 binding protein (IL-18BP), a high-affinity endogenous antagonist that limits the free, bioactive cytokine fraction. This review re-examines the IL-18/IL-18BP axis across a clinical gradient from barrier dysfunction and allergic disease, through systemic autoimmunity, to Still disease, macrophage activation syndrome, hemophagocytic lymphohistiocytosis, and monogenic IL-18opathies. We emphasize that total IL-18 elevation does not necessarily imply pathogenic IL-18 activity; the key translational question is whether IL-18BP-mediated restraint remains sufficient. In barrier disorders and systemic autoimmunity, IL-18 often behaves as a contextual amplifier or biomarker-amplifier axis. In hyperinflammatory and selected monogenic disorders, extreme IL-18 production may exceed endogenous antagonism, allowing free IL-18 to emerge and acquire diagnostic, mechanistic, and therapeutic relevance. Interpreting total IL-18, IL-18BP/free IL-18, and downstream IFN-γ/CXCL9 signals together may improve biomarker interpretation and guide rational targeting of the pathway.},
DOI = {10.32604/ecn.2026.083788}
}