IL-6 and IL-6 Receptor Proteins

In 1973, Interleukin 6 (IL-6) was identified as a soluble factor secreted by T cells, which is essential for the production of antibodies by B cells. Since its discovery nearly 50 years ago, the IL-6 signaling pathway has emerged as a key pathway involved in immune regulation in health and immune dysregulation in many diseases.

In the classical pathway, IL-6 binds to the membrane-bound IL-6 receptor (IL-6R), and this complex subsequently associates with gp130, triggering downstream signaling. In the trans-signaling pathway, IL-6 binds to the soluble form of its receptor (IL-6R), and this IL-6/IL-6R complex then binds to gp130 to initiate intracellular signaling. In the next step, the JAK-STAT, RAS-RAF, and other pathways are activated, promoting cellular proliferation, differentiation, oxidative stress, and immune regulation. The classical IL-6 signal is limited to the cells (macrophages, neutrophils, T cells, etc.) that express IL-6R. But when IL-6 levels are elevated, the signal is widely expressed due to the ubiquitous nature of gp130.

IL-6 signaling pathway

Furthermore, emerging evidence suggests that dysregulation of IL-6 contributes to a variety of disease states, including various types of cancer development, progression, and metastasis, increased levels of IL-6 are associated with a higher risk of cancer and other diseases, such as insulin resistance, asthma, coronary heart disease, advanced cancer, and can also serve as a prognostic marker for cancer. Targeting this pathway may expand to the treatment of several other symptoms, such as uveitis, neuromyelitis optica, and more recently, COVID-19 pneumonia.

ACROBiosystems has developed a series of high-quality IL-6 and IL-6 receptor proteins to facilitate the development of IL-6 related drugs.

Product Features

Human and Mouse species are available

High purity: >95%

High bioactivity verified by ELISA, BLI and cell-based assay. Free protocols offered

Various tags:Tag Free,His Tag,Avi & His Tag,Fc Tag

Low endotoxin:< 1.0 EU/μg

Product List

IL-6
IL-6 R alpha
IL-6 R beta

Verification Data

High purity is more than 95% as verified by SDS-PAGE

High purity is more than 95% as verified by SDS-PAGE

Biotinylated Human IL-6 R alpha, Avitag, His Tag (Cat. No. CD6-H82E8) on SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%. The protein has a calculated MW of 41.7 kDa and migrates as 55-70 kDa due to glycosylation.

High bioactivity verified by ELISA

High purity is more than 95% as verified by SDS-PAGE

Immobilized ActiveMax® Human IL-6, Tag Free (Cat. No. IL6-H4218) at 5 μg/mL (100 μL/well) can bind Biotinylated Human IL-6 R alpha, Avitag, His Tag (Cat. No. CD6-H82E8) with a linear range of 4-125 ng/mL.

High bioactivity verified by BLI

High purity is more than 95% as verified by SDS-PAGE

Loaded Human IL-6 R alpha, Fc Tag (Cat. No. ILR-H5259) on Protein A Biosensor, can bind ActiveMax® Human IL-6, Tag Free (Cat. No. IL6-H4218) with an affinity constant of 35.9 nM as determined in BLI assay (ForteBio Octet Red96e).

High bioactivity verified by cell-based assay

High purity is more than 95% as verified by SDS-PAGE

ActiveMax® Human IL-6, Tag Free (Cat. No. IL6-H4218) stimulates proliferation of TF-1 human erythroleukemic cell line. The EC50 for this effect is 0.2856-0.3636 ng/mL.

High purity is more than 95% as verified by SDS-PAGE

Biotinylated Human IL-6, epitope tag free, primary amine labeling (Cat. No. IL6-H8218) stimulates proliferation of TF-1 human erythroleukemic cell line. The EC50 for this effect is 0.2532-0.4489 ng/mL.

Related Reading

>>【Inspiring Target】Therapeutic potential of IL-6 immunization in multiple fields continues to burst

References

1. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol 16, 335–345 (2020).

  • Authors:Choy, E.H., De Benedetti, F., Takeuchi, T. et al.

2. IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy?. Pharm Med 34, 223–231 (2020).

  • Authors:Atal, S., Fatima, Z.

3. Computer-aided prediction and design of IL-6 inducing peptides: IL-6 plays a crucial role in COVID-19. Briefings in Bioinformatics. 2021, 22(2): 936–945.

  • Authors:Anjali Dhall et al.

4. Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis. JAMA. 2021, 326(6):499–518.

  • Authors: The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.

5. Why tocilizumab could be an effective treatment for severe COVID-19?. J Transl Med 18, 164 (2020).

  • Authors:Fu, B., Xu, X. & Wei, H.

FAQ

Q

Why is it important to distinguish IL-6 classic signaling from trans-signaling during drug development?

In classic signaling, IL-6 binds membrane IL-6Rα and recruits gp130, so responsiveness is largely restricted to cells expressing IL-6Rα. In trans-signaling, IL-6 complexes with soluble IL-6Rα and can activate gp130 on a broader range of cells. Therapeutics that neutralize IL-6, block IL-6Rα, or selectively disrupt trans-signaling may therefore differ in pathway coverage, tissue effects, and safety profile. Assays should be selected to match the intended mechanism.
Q

Why should gp130-family pathway selectivity be assessed when developing IL-6 inhibitors?

gp130 is the signal-transducing subunit used by several IL-6-family cytokines, not only IL-6. A candidate directed at gp130 or at cytokine–receptor complex assembly may therefore affect related pathways depending on its epitope and mechanism. Selectivity assessment should compare IL-6–IL-6Rα–gp130 activity with other relevant gp130-family ligand systems. This helps distinguish IL-6-selective inhibition from broader suppression of shared cytokine signaling.
Q

Why are correct folding and glycosylation of IL-6Rα and gp130 important for antibody screening?

IL-6Rα and gp130 are glycosylated extracellular receptors whose folding and disulfide bonding influence ligand binding and antibody epitope presentation. Glycosylation can also make the apparent SDS-PAGE molecular weight higher than the calculated value, so this shift should not automatically be interpreted as aggregation or impurity.
Q

How does selective inhibition of IL-6 trans-signaling differ from pan-IL-6 or IL-6R blockade?

Pan-IL-6 or IL-6R blockade can suppress both classic and trans-signaling, whereas a trans-signaling-selective strategy is designed to interfere mainly with IL-6–soluble IL-6Rα complexes. These approaches may produce different effects on inflammatory pathology and physiological IL-6 functions. Candidate characterization should therefore include assays representing membrane IL-6Rα signaling and soluble IL-6Rα-dependent signaling rather than relying on a single ligand–receptor binding test.
Q

Which quality and activity data are most informative when selecting IL-6 pathway proteins?

Useful evidence includes purity, molecular homogeneity, endotoxin level where cell assays are planned, and binding activity for the intended ligand–receptor pair. For IL-6 itself, a relevant cell-based assay such as TF-1 proliferation provides additional confirmation of functional potency. SEC-MALS, ELISA, SPR, or BLI data are valuable when available, but quality packages vary by product. Final selection should be based on the individual product page and lot-specific documentation.
  • Background
  • Product Features
  • Product List
  • Verification Data
  • References
  • FAQ