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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.
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.
In plain words · 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.
Backbone ribbon from PDB 8J6F. RCSB PDB 8J6F. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
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.
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.
2 products aim at Interleukin-6 and IL-6 receptor: antibodies. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
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.)
Sources: Human Protein Atlas IL6 tissue; Human Protein Atlas IL6R tissue; UniProt P05231; UniProt P08887; Open Targets ENSG00000136244 associations; Open Targets ENSG00000160712 associations
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.
RNA: tissue enhanced (adipose tissue 188 nTPM, lung 141 nTPM, urinary bladder 256 nTPM), detected in many normal tissues. Blood: lineage enriched (B-cells 5 nTPM).
No normal tissue stained high; medium in Bone marrow, Lymph node, Tonsil.
No cancer stained high; medium in endometrial cancer.
HPA IL6 tissue · HPA IL6 pathology · HPA protein class: FDA approved drug targets
RNA: tissue enhanced (liver 59 nTPM, skeletal muscle 91 nTPM), detected in all normal tissues.
No normal tissue stained high.
No cancer sample stained medium or high.
HPA IL6R tissue · HPA IL6R pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Multiple myeloma | 35% | Detectable serum IL-6 by bioassay in 85 patients with overt multiple myeloma | 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 | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Siltuximab (Sylvant) is an antibody that neutralises the inflammatory messenger interleukin-6. It is the only approved treatment for multicentric Castleman disease, a rare lymph node disorder, in people without HIV or HHV-8 infection.
Tocilizumab (Actemra) is a rheumatoid arthritis antibody that has become the rescue drug for cytokine release syndrome, the fever and blood-pressure crash that CAR-T cells and bispecific antibodies can trigger. Every CAR-T centre must have it on hand.
The myCAF and iCAF distinction is why 'target the stroma' became 'target a fibroblast state', and IL-6 blockade combinations follow from it.
This paper is the molecular sequel to the 2002 inflammation and cancer review and the basis for IL-6, JAK-STAT and NF-kB directed strategies in cancer as well as for aspirin and other anti-inflammatory prevention trials.
Query for this target: (TITLE:"Interleukin-6 and IL-6 receptor" OR ABSTRACT:"Interleukin-6 and IL-6 receptor" OR TITLE:"IL6" OR ABSTRACT:"IL6" OR TITLE:"IL6R" OR ABSTRACT:"IL6R") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Interleukin-6 and IL-6 receptor, not a curated reading list.
Shares Siltuximab, Multiple myeloma.
Shares Siltuximab, Multiple myeloma.
Shares Tocilizumab, T-cell engagers (bispecific), Multiple myeloma.
Shares T-cell engagers (bispecific), CAR-T cell therapy, Multiple myeloma.
Shares Tocilizumab, T-cell engagers (bispecific).
Shares Tocilizumab, Multiple myeloma.
Shares Tocilizumab, T-cell engagers (bispecific).
Shares Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer, Microenvironment and inflammation: tumours as wounds that do not heal.