IL-6 (Interleukin 6) Basics

IL-6 (interleukin 6), originally discovered as a B-cell differentiation factor, is a multifunctional pleiotropic cytokine that regulates immune response, acute-phase response, hematopoiesis, and inflammation.
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In the following, we will mainly discuss IL-6 (interleukin 6) & receptor, IL-6 (interleukin 6) function, IL-6 (interleukin 6) inflammation and anti IL-6 (interleukin 6) monoclonal antibody.

IL-6 (Interleukin 6) & Receptor

IL-6 (interleukin 6) is a member of the IL-6 family, including, among others, leukemia inhibitory factor (LIF), ciliary neurotrophic factor, and oncostatin-M (OSM). The human gene of IL-6 maps to locus 7p2; the murine IL-6 is located on chromosome 5. Human and murine IL-6 contains 5 exons and 4 introns.

IL-6 (interleukin 6) receptor consists of an IL-6 receptor subunit (IL6R) and interleukin 6 signal transducer gp130 (also known as IL6ST). Gp130 possesses a WSXWS amino acid motif that ensures correct protein folding and ligand binding.

IL-6 (Interleukin 6) Function

IL-6 (interleukin 6) functions as a mediator for notification of the occurrence of some emergent event. IL-6 is generated in an infectious lesion and sends out a warning signal to the entire body. The signature of exogenous pathogens, known as pathogen-associated molecular patterns, is recognized in the infected lesion by pathogen-recognition receptors (PRRs) of immune cells such as monocytes and macrophages.

IL-6 also issues a warning signal in the event of tissue damage. Damage-associated molecular patterns (DAMPs), which are released from damaged or dying cells in noninfectious inflammations such as burn or trauma, directly or indirectly promote inflammation.

IL-6 (Interleukin 6) Inflammation

IL-6 (interleukin 6), promptly and transiently produced in response to infections and tissue injuries, plays a key role in both acute and chronic inflammation.

IL-6 is the chief stimulator of the production of most acute phase proteins, whereas the other implicated cytokines influence subgroups of acute phase proteins. The main switch from acute to chronic inflammation is the recruitment of monocytes to the area of inflammation. IL-6 is important to the transition between acute and chronic inflammation.

IL-6 exhibits two contrasting features. In models of chronic inflammatory diseases, such as collagen-induced arthritis, murine colitis, or experimental autoimmune encephalomyelitis, IL-6 is proinflammatory, whereas in models of acute inflammation IL-6 exhibits an anti-inflammatory profile.

IL-6 levels are elevated in inflammatory diseases in humans. Expression of IL-6 is enhanced at the site of inflammation, and blockade of IL-6 and IL-6 signalling is effective at prevention and treatment in models of inflammatory diseases (including arthritis and colitis).

Anti IL-6 (Interleukin 6) Monoclonal Antibody

The chronology of clinical investigations of monoclonal antibody to IL-6 in the treatment of cancer and related lymphoproliferative disorders spans roughly a decade, beginning with the first report of a single patient with plasma cell leukemia (PCL) who was treated with mAb to IL-6 in 1991.
Siltuximab, an anti-IL6 chimeric monoclonal antibody, binds to IL-6 (interleukin 6). Siltuximab receives FDA approval to treat multicentric castleman's disease (MCD) in 2014.
Several other promising IL-6 blocking agents are currently undergoing clinical trials.

References

1. Akdis, M., Burgler, S., Crameri, R., Eiwegger, T., Fujita, H., Gomez, E., ... & Rhyner, C. (2011). Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. Journal of allergy and clinical immunology, 127(3), 701-721.
2. Gabay, C. (2006). Interleukin-6 and chronic inflammation. Arthritis research & therapy, 8(2), S3.
3. Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harbor perspectives in biology, 6(10), a016295.