Review of the potential value of serum interleukin levels as prognostic biomarkers of liver failure

Figure 1 Mechanism of interleukin 21 in liver failure (diagram depicts various immune cells, including CD4+ T cells, natural killer cells, B cells, T cells, and dendritic cells, along with their interactions and functions). The central role of interleukin 21 (IL-21) is highlighted, as it is secreted by CD4+ T cells and influences the differentiation of B cells into plasma cells, leading to immunoglobulin production, while also inhibiting T cell survival and generation. Additionally, IL-21 can stimulate dendritic cells to induce apoptosis, further impacting the immune response). APC: Anaphase-promoting complex; IFN-γ: Interferon gamma.

Figure 2 Molecular mechanisms underlying the involvement of interleukin 21 (IL-21), IL-22, and IL-31 in liver failure (diagram depicts the signaling pathway of ILs and their involvement in liver failure). It starts with a CD4+ T cell or immune cell at the top, which secretes three different types of interleukin (IL): IL-21, IL-22, and IL-31. Each IL binds to its specific receptor on the cell surface: IL-21 binds to the IL-21 receptor (IL-21R), IL-22 binds to the IL-10R2 and IL-22R1, and IL-31 binds to the IL-31RA and oncostatin M receptor (OSMR). These receptors activate downstream signaling pathways involving Janus kinase 1 (JAK1), JAK2, JAK3, and tyrosine kinase 2 (TYK2), which phosphorylate signal transducer and activator of transcription (STAT) proteins. The activated STAT proteins then translocate to the nucleus and regulate gene expression, activating phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways. The diagram shows that these signaling events ultimately lead to liver failure through various mechanisms, including increased levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin [TBIL], alpha-fetoprotein [AFP], model for end-stage liver disease [MELD]), liver cirrhosis, hepatitis B, and liver fibrosis, which highlights the complex interplay between immune cells, ILs, and signaling pathways in the pathogenesis of liver failure.) APAP: Acetaminophen; CCl4: Carbon tetrachloride; ConA: Concanavalin A; LPS: Lipopolysaccharides.

Figure 3 Mechanism of interleukin 22 (IL-22) in liver failure (diagram illustrates the protective role of IL-22 in liver health and its potential benefits in preventing liver failure). Interleukin 22 (IL-22) is secreted by immune cells, specifically progenitor cells, and binds to receptors on the surface of hepatocytes, stellate cells, and progenitor cells. This binding triggers a series of downstream effects: (1) Hepatocytes: IL-22 acts on hepatocytes by increasing the production of acute-phase proteins, which help fight infection and inflammation. This, in turn, helps restrain the infiltration of immune cells, reducing inflammation and protecting the liver from damage; (2) Stellate cells: IL-22's interaction with stellate cells increases protection against damage and reduces liver cell apoptosis (cell death) and oxidative stress; (3) Progenitor cells: IL-22 stimulates the production of mitochondria and antioxidant proteins in progenitor cells. This promotes the proliferation of liver progenitor cells and hepatic stem cells, which are crucial for liver regeneration).