IL6 Specific Neutra™ Antibody Products
Product listInterleukin-6 (IL-6) was originally identified as B cell stimulating factor 2 (BSF-2), which promotes immunoglobulin synthesis by activated B cells. It is a 26 kDa glycoprotein composed of 184 amino acids. IL-6 is a typical cytokine and has a wide range of biological effects on immune cells and many other cells. It is involved in the growth of tumors, the malignant differentiation of cancer cells and the regulation of immune microenvironment.
IL-6, a Pleiotropic Cytokine
IL-6 exerts various biological effects on different target cells and organs. At the site of infection or injury, innate immune cells rapidly produce IL-6 by recognizing molecules of pathogen-associated molecular patterns or injury-associated molecular patterns, triggering an innate immune response. IL-6 is also important for adaptive immune response by promoting differentiation of B and T cells. The other functions of IL-6 are to promote follicular helper t cell differentiation and IL-21 production, as well as to induce cytotoxic CD8+ T cell differentiation by enhancing the expression of IL-2 and its receptors. IL-6 also participates in bone homeostasis.
Fig.1 The pleiotropic effects of IL-6.1
IL-6 Signaling
Targeting the IL-6 signaling pathway is a new strategy, among which tissue inhibitor of metalloproteinase-3 (TIMP-3) is a potential target. Neutralizing IL-6 antibodies have been used to block JAK1-STAT3 signaling in lung cancer models. The signal transduction mediated by IL6 may be blocked by directly inhibiting IL6 or IL6R using monoclonal antibodies. Three different types of IL-6 signaling are as follows:
- For signal transduction to occur, IL-6 must first bind the IL-6 receptor (IL-6R), after which the resultant complex must associate with a second protein called glycoprotein 130 (gp130). The signaling mediated by IL-6 through its membrane-bound cognate receptor is called classical signaling.
- IL-6 can also bind to the soluble form of IL-6R before aggregation to gp130 (trans-signaling).
- IL-6 can transpose from dendritic cells to T cells via its membrane-bound IL-6R (trans-presentation).
In general, classical signaling causes physiological, anti-inflammatory, and pro-resolving effects of IL-6, whereas trans-signaling and trans-presentation mediate pathological effects of cytokines. Importantly, there is a monoclonal antibody against IL-6R that does not distinguish between these signaling types but blocks all IL-6 signaling.
Fig.2 The different types of IL-6 signaling.1
The Anti-IL6 Drugs
A variety of monoclonal antibodies (mAbs) against IL6 have been developed. A chimeric anti-IL6 mAb has been used in clinical trials for the treatment of multiple myeloma, metastatic renal cancer, and prostate cancer, and has recently been registered for the treatment of patients with Castleman's disease. Another humanized anti-IL6 mAb, has been tested for PK/PD and safety in healthy subjects. Effective antagonists of the IL6 receptor have been designed by amino acid substitutions targeting key residues of the human IL6 molecule. Anti-IL6R mAb has been tested in immune dysregulation disorders.
Diseases Improved by Anti-IL6 Therapies
The current treatment methods include mAbs that directly block ligands or receptors, recombinant cytokine regimens, or small molecule drugs that interfere with downstream signaling.
- Dysimmune Diseases
Anti-IL6 therapy has been developed for the treatment of immune disorders and cancer. The current IL6 inhibitors include mAbs targeting IL6 or IL6 receptors. The development of chronic inflammation and/or autoimmune diseases can be prevented or treated by knocking out genes or administering IL6 blocking with anti-IL6 or anti-IL6R antibodies.
- Castleman Disease
Castleman's disease is a lymphoproliferative disorder mainly caused by viral IL6. BE-8 anti-IL6 murine mAb has been used for the first time in a patient with Castleman's disease, and the patient's condition is observed to be improved significantly after treatment. The rationale for the development of anti-IL6 therapies is that IL6 is a major growth factor for plasmablast cells and has pleiotropic activity, which may explain vascular proliferation in particular.
Creative Biolabs offers nearly ninety different anti-IL6 antibody products. These antibodies are recombinantly expressed and could be used in eleven applications. Customization of IL6-based bispecific antibodies is also available for you here.
REFERENCE
- McElvaney, Oliver J., et al. "Interleukin-6: obstacles to targeting a complex cytokine in critical illness." The Lancet Respiratory Medicine 9.6 (2021): 643-654.
