Structure of IL-6

IL-6 is a 19–26 kDa pleiotropic cytokine composed of 212 amino acids. It has a four-helix bundle structure with two long and two short α-helices, stabilized by two disulfide bonds. IL-6 is mainly produced by immune cells (macrophages, T cells, B cells), fibroblasts, and endothelial cells in response to infection, inflammation, or stress.

Receptor Components

IL-6 signaling is mediated through a two-component receptor complex:

1. IL-6R (CD126): A membrane-bound or soluble receptor that specifically binds IL-6.
2. gp130 (CD130): A signal-transducing subunit that activates downstream pathways.
3. Function of IL-6

IL-6 is a key cytokine in immune regulation, inflammation, hematopoiesis, and metabolism.

• Pro-inflammatory Role: Triggers acute-phase response, promotes fever, and induces CRP production.
• Anti-inflammatory Role: Regulates tissue repair and suppresses excessive immune responses.
• Hematopoiesis: Supports B-cell differentiation, T-cell activation, and megakaryocyte maturation.
• Metabolism: Regulates glucose homeostasis and lipid metabolism in liver and muscle tissues.
• Cancer Progression: Elevated IL-6 levels are associated with cancer proliferation, angiogenesis, and metastasis.

IL-6 Signaling Pathway

IL-6 signaling occurs via three main pathways:

(A) Classical Signaling (Protective Role)

• Receptor Binding: IL-6 binds to membrane-bound IL-6R, forming a complex with gp130.
• JAK-STAT Activation: Janus kinases (JAK1, JAK2, Tyk2) phosphorylate gp130, activating STAT3, which translocates to the nucleus to regulate gene expression.
• Effects: Supports tissue regeneration, immune balance, and normal inflammatory responses.

(B) Trans-Signaling (Pro-inflammatory Role)

• Soluble IL-6R (sIL-6R)binds IL-6, interacting with gp130-expressing cells that do not have IL-6R.
• This pathway is linked to chronic inflammation, autoimmunity, and cancer progression.

(C) Trans-Presentation

• IL-6 is presented by dendritic cells to T cells via IL-6R and gp130, regulating T-cell differentiation.

Market Prospects of IL-6 Targeting Drugs

• Global Market Size: Estimated at $10.5 billion in 2023, projected to grow at 2% CAGR.
• Key Drivers: Rising cases of autoimmune diseases (RA, lupus), cytokine storm management (COVID-19), and oncology applications.
• Key Companies: Roche, Sanofi, Novartis, Johnson & Johnson, Pfizer.

Future Trends:

• Bispecific antibodiestargeting IL-6 and TNF-α or IL-6 and IL-17.
• Oral IL-6 inhibitorsunder development.
• Personalized therapybased on cytokine profiling.

FDA-Approved IL-6 Targeting Drugs

IL-6 inhibitors continue to gain traction, with emerging indications in oncology, neuroinflammation, and cardiovascular diseases.

Our IL-6 Related Antibody Products