{"entity":{"id":"il6","kind":"target","name":"Interleukin-6 and IL-6 receptor","aka":[],"tldr":"Interleukin-6 is an inflammation messenger. Blocking it treats Castleman disease, a lymph node disorder, and calms the dangerous immune storm that CAR-T cell therapy can trigger.","summary":"Interleukin-6 is a pleiotropic cytokine signalling through the IL-6 receptor and gp130 to activate JAK-STAT3. In oncology it is targeted in two ways: siltuximab (anti-IL-6) is approved for idiopathic multicentric Castleman disease, where IL-6 drives the lymphoproliferation and systemic symptoms, and tocilizumab (anti-IL-6 receptor) is approved to treat severe or life-threatening cytokine release syndrome after CAR-T cell therapy and bispecific T-cell engagers. IL-6 also mediates cancer cachexia and tumour-promoting inflammation, and STAT3 activation downstream is a therapeutic target in its own right.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Interleukin_6","links":[{"label":"NCBI Gene IL6","url":"https://www.ncbi.nlm.nih.gov/gene/3569"}],"tags":["cytokine"],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t","t-cell-engager"],"targets":[],"drugs":["siltuximab","tocilizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["The myeloma row is a serum-cytokine measure, not tumour expression: IL-6 is produced largely by the marrow microenvironment and no approved IL-6 or IL-6R antibody is selected on IL-6 level.","Pancreatic ductal adenocarcinoma: IL-6 is the signature secretion of the inflammatory fibroblast state (iCAF) that sits away from the tumour cells, distinct from the myofibroblastic state that builds the desmoplastic stroma (Ohlund 2017)."],"symbol":"IL6, IL6R","role":[],"sources":[],"specificity":"immune-microenvironment","distribution":"one-type","specificityNote":"Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA IL6: RNA tissue enhanced (adipose tissue 188 nTPM, lung 141 nTPM, urinary bladder 256 nTPM); blood lineage lineage enriched (B-cells 5 nTPM); no normal tissue stained high. HPA IL6R: RNA tissue enhanced (liver 59 nTPM, skeletal muscle 91 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Multiple myeloma); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas IL6 tissue","url":"https://www.proteinatlas.org/ENSG00000136244-IL6/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas IL6R tissue","url":"https://www.proteinatlas.org/ENSG00000160712-IL6R/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt P05231","url":"https://www.uniprot.org/uniprotkb/P05231/entry","note":"involvement in disease"},{"label":"UniProt P08887","url":"https://www.uniprot.org/uniprotkb/P08887/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000136244 associations","url":"https://platform.opentargets.org/target/ENSG00000136244/associations","note":"cancer associations at or above 0.5 (CC0)"},{"label":"Open Targets ENSG00000160712 associations","url":"https://platform.opentargets.org/target/ENSG00000160712/associations","note":"cancer associations at or above 0.5 (CC0)"}],"biology":"Classic signalling via membrane IL-6R on hepatocytes and leukocytes; trans-signalling via soluble IL-6R broadens the responsive cell range. IL-6 blockade masks fever and CRP, so infection surveillance must rely on other signs.","whereFound":["Multicentric Castleman disease","Cytokine release syndrome after CAR-T or bispecific therapy","Cancer cachexia","Multiple myeloma microenvironment"],"targetClass":"other","prevalence":[{"cancerId":"multiple-myeloma","pct":35,"measure":"Detectable serum IL-6 by bioassay in 85 patients with overt multiple myeloma","source":"https://doi.org/10.1172/JCI114392","note":"Bataille 1989 (J Clin Invest); 37% at diagnosis, 13% in stable disease, 60% in fulminating disease, 100% of 11 plasma cell leukaemias and 3% of MGUS/smouldering myeloma"}]},"route":"/targets/il6/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"drug":[{"id":"siltuximab","kind":"drug","name":"Siltuximab","route":"/drugs/siltuximab/"},{"id":"tocilizumab","kind":"drug","name":"Tocilizumab","route":"/drugs/tocilizumab/"}],"paper":[{"id":"paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017","kind":"paper","name":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","route":"/key-papers/paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017/"},{"id":"paper-grivennikov-immunity-inflammation-cancer-cell-2010","kind":"paper","name":"Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer","route":"/key-papers/paper-grivennikov-immunity-inflammation-cancer-cell-2010/"}],"term":[{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","route":"/terms/microenvironment-inflammation-theory/"}]}}