Immune regulatory cytokine that acts as a suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. Signaling can occur via two mechanisms, intracellularly through nuclear translocation with SMAD3 and extracellularly after secretion and binding to its receptor composed of IL18R1 and IL18RAP. Suppresses, or reduces, pro-inflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation. Interacts with SMAD3. Binds IL18R1, but not to IL1R1, with lower affinity than IL18, and does not seem to act as a receptor antagonist for IL18. Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059). Stimulation with IL1B leads to colocalization with SMAD3 mostly in perinuclear regions (PubMed:20935647, PubMed:33674380). Only the CASP1-cleaved mature form translocates into the nucleus upon LPS stimulation (PubMed:18390730). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059, PubMed:33674380). In general, low constitutive expression, if any, in healthy tissues; high expression in inflammatory counterparts, including in synovial tissues from individuals with active rheumatoid arthritis. Isoform A, isoform B and isoform C are expressed in testis, colon, placenta, lung and lymph node. Isoform D and isoform E were found only in testis and bone marrow. Whereas only isoform A is found in brain, only isoform B in kidney and only isoform C in heart. Highly induced by bacterial lipopolysaccharides (LPS) and TGFB1, more moderately by IFNG, IL18, IL1B, TNF and the dinucleotide CpG (at protein level). Constitutive expression in bone marrow macrophages is down-regulated in the presence of IL4 and CSF2. Induced by phorbol myristate acetate (PMA) in different cell lines. Proteolytically converted to the mature form by CASP1. The disease is caused by variants affecting the gene represented in this entry. The name IL-HL refers to isoform B containing polymorphisms Val-31 and Ala-42. Belongs to the IL-1 family. Interleukin-1 entry