Interleukin-6 and IL-6 receptor

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.

Interleukin-6 and IL-6 receptor: what it is and how drugs act on it · animated generic schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

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.

1 · What it is
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.
2 · What goes wrong in cancer
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.
3 · How drugs use it
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.

Full dossier: hotspots, trials, resistance, assays, models, open questions →

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 it is found

Multicentric Castleman disease
Cytokine release syndrome after CAR-T or bispecific therapy
Cancer cachexia
Multiple myeloma microenvironment

Class

other · IL6, IL6R

Products

2top

ApprovedMonoclonal antibody (anti-IL-6, chimeric IgG1)

Siltuximab · Sylvant

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.

ApprovedMonoclonal antibody (anti-IL-6 receptor, humanised IgG1)

Tocilizumab · Actemra

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.