急性膵炎におけるインターロイキン-22：損傷と修復のバランス

Acute pancreatitis (AP) is a severe inflammatory disorder characterized by the premature activation of digestive enzymes, acinar cell injury, and systemic complications. Interleukin-22 (IL-22), a member of the IL-10 cytokine family, has increasingly been recognized as a critical mediator at the intersection of immune regulation and epithelial protection. Experimental evidence indicates that IL-22 exerts both protective and pathogenic effects depending on disease stage and immune context.

This review synthesized findings from experimental and clinical studies investigating the role of IL-22 in AP. Literature encompassing murine models, in vitro experiments, and patient cohorts, was analyzed, with emphasis on signaling mechanisms, tissue-protective versus pathogenic functions, and the translational potential of IL-22 as both a therapeutic target and a biomarker.

IL-22 safeguards acinar cells through signal transducer and activator of transcription 3 and AKT/mTOR signaling, suppresses excessive autophagy, and promotes the expression of anti-apoptotic proteins (Bcl-2, Bcl-xL). It strengthens intestinal barrier integrity via Reg-IIIβ/γ induction, reduces lung injury by limiting neutrophilic inflammation, and shows hepatoprotective and renoprotective properties. Elevated serum IL-22 levels in patients with severe AP correlate with gastrointestinal failure and systemic complications, supporting its utility as a biomarker. Nonetheless, IL-22 exhibits dual roles: in mild AP, it can exacerbate necrosis, while chronic activity has been linked to fibrosis and tumorigenesis. Regulation by IL-22 binding protein (IL-22BP) is essential for maintaining homeostasis. Preclinical nanotherapeutic strategies have improved IL-22 delivery and stability.

IL-22 constitutes both a promising therapeutic candidate and a potential biomarker in AP. Recombinant IL-22 and advanced delivery systems can reduce complications in severe disease, while IL-22 measurement could improve prognostic stratification. However, key challenges remain concerning safety, optimal therapeutic windows, and long-term risks. Large-scale clinical trials are required to establish IL-22 as a cornerstone of precision medicine in AP.