# Interleukin-6 and IL-6 receptor

Source: https://onco.cc/targets/il6/  
OnCo record `il6` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-09-10
- Tags: cytokine
- Symbol: IL6, IL6R
- Class: other
- 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.
- Where found: Multicentric Castleman disease; Cytokine release syndrome after CAR-T or bispecific therapy; Cancer cachexia; Multiple myeloma microenvironment

## 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).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Interleukin_6
- NCBI Gene IL6: https://www.ncbi.nlm.nih.gov/gene/3569

## Connected records

- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- drugs: [Siltuximab](https://onco.cc/drugs/siltuximab/), [Tocilizumab](https://onco.cc/drugs/tocilizumab/)
- key papers: [Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer](https://onco.cc/key-papers/paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017/), [Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer](https://onco.cc/key-papers/paper-grivennikov-immunity-inflammation-cancer-cell-2010/)
- terms: [Microenvironment and inflammation: tumours as wounds that do not heal](https://onco.cc/terms/microenvironment-inflammation-theory/)

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