IL6

Synonyms

B-cell stimulatory factor 2, Interferon beta-2, IL6, IFNB2, IL-6, Interleukin-6, Interleukin 6, Hybridoma Growth Factor, IFN-Beta-2, BSF-2, CDF, B-Cell Differentiation Factor, Interferon, Beta 2, Interleukin BSF-2, BSF2, HGF, HSF, CTL Differentiation Factor, Interleukin 6 (Interferon, Beta 2)

Description

Interleukin-6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene.Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (Probable). In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4 T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4 T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells.Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability . Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF . Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance . 'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis. Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. Also acts as a myokine (Probable). Plays a protective role during liver injury, being required for maintenance of tissue regeneration. Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection . Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration.

KO Status

F2 (-/-)

Drug Information

Launched drugs: 5
Drugs in clinical trials: 18
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Lenalidomide

IMID-5013, CDC-5013, CDC-501, ENMD-0997, CC-5013, IMiD-3

Approved

Celgene Corp

Leukemia, Myeloid, Lymphoma, T-Cell, Peripheral, Lymphoma, B-Cell, Marginal Zone, Hematologic Diseases, Solid tumours, HIV Infections, Lymphoma, B-Cell, Anemia, Paraproteinemias, Leukemia-Lymphoma, Adult T-Cell, Blood Protein Disorders, Myelodysplastic Syndromes, Lymphoma, Large B-Cell, Diffuse, Smoldering Multiple Myeloma, Multiple Myeloma, Lymphoma, Mantle-Cell, Radiculopathy, Reflex Sympathetic Dystrophy, Lymphoma, Follicular, Prostatic Neoplasms, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell, Leukemia, Myeloid, Acute, Thrombocytopenia, Waldenstrom Macroglobulinemia, Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Complex Regional Pain Syndromes, Melanoma, Neoplasm Metastasis, Crohn Disease, Carcinoma, Non-Small-Cell Lung

Luminol sodium

MP-1032

Approved

Selvim, Metrio

Immune System Diseases, Psoriasis

Pomalidomide

CDC-394, CC-4047, IMiD-1, IMID-4047

Approved

Celgene Corp

Medulloblastoma, Solid tumours, Bone Marrow Neoplasms, Lymphoma, B-Cell, Scleroderma, Systemic, Hodgkin Disease, Lymphoma, Large B-Cell, Diffuse, Multiple Myeloma, Lung Diseases, Interstitial, Central Nervous System Neoplasms, Sarcoma, Prostatic Neoplasms, Lymphoma, Follicular, Primary Myelofibrosis, Lymphoma, Non-Hodgkin, Neoplasm Metastasis, Leukemia, Lymphocytic, Chronic, B-Cell, Sarcoma, Kaposi, Anemia, Sickle Cell

Siltuximab

cCLB-8, CNTO-328

Approved

Eusa Pharma, Janssen Global Services Llc

Respiratory Tract Infections, Head and Neck Neoplasms, Ovarian Neoplasms, Carcinoma, Renal Cell, Pneumonia, Smoldering Multiple Myeloma, Pancreatic Neoplasms, Myelodysplastic Syndromes, Lung Diseases, Respiratory Distress Syndrome, Adult, Multiple Myeloma, Monoclonal Gammopathy of Undetermined Significance, Multicentric Castleman's Disease (MCD), Prostatic Neoplasms, Neoplasms, Plasma Cell, Colorectal Neoplasms, Castleman Disease, Lung Neoplasms, Lymphoma, Non-Hodgkin

Thalidomide

K-17, NSC-66847, NSC-527179

Approved

Celgene Corp

HIV Infections, Myelodysplastic Syndromes, Spondylitis, Ankylosing, Multiple Myeloma, Erythema Nodosum, HIV Wasting Syndrome, Leprosy, Lepromatous, Carcinoma, Hepatocellular

Sirukumab

BA-003, CNTO-136

NDA/BLA

Glaxosmithkline Plc, Janssen Global Services Llc

Giant Cell Arteritis, Depressive Disorder, Major, Lupus Erythematosus, Cutaneous, Arthritis, Rheumatoid, Lupus Nephritis, Polymyalgia Rheumatica, Lupus Erythematosus, Systemic, Asthma

Mycobacterium cell wall-DNA Complex (ProMetic Life Sciences)

EN-3348

NDA/BLA

Prometic Life Sciences

Neoplasm Recurrence, Local, Urinary Bladder Neoplasms, Carcinoma in Situ

CD24-Fc

HAS-CD24, CD24-Fc-IgG, MK-7110, MK7110, CD24-Fc

Phase 3 Clinical

Oncoimmune

Leukemia, HIV Infections, Hematopoietic stem cell transplantation (HSCT), Graft vs Host Disease, Coronavirus Disease 2019 (COVID-19), Myelodysplastic Syndromes, Dyslipidemias, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Melanoma

Olokizumab

CDP-6038, Anti-IL6-UCB

Phase 3 Clinical

Ucb

Arthritis, Rheumatoid, Coronavirus Disease 2019 (COVID-19), Arthritis, Crohn Disease

Clazakizumab

ALD-518, ALD518-003, BMS-645429, BMS-945429

Phase 3 Clinical

Alder Biopharmaceuticals

Anemia, Graft vs Host Disease, Arthritis, Rheumatoid, Fatigue, Rejection of organ transplantation, Arthritis, Psoriatic, Inflammation, Cachexia, Carcinoma, Non-Small-Cell Lung, Crohn Disease, Stomatitis

References

Title

Authors

Source

SorLA in Interleukin-6 Signaling and Turnover

Larsen J.V., Petersen C.M.,

Mol. Cell. Biol. 37:0-0(2017)

Targeting Interleukin-6 Signaling in Clinic

Kang S., Tanaka T., Narazaki M., Kishimoto T.,

Immunity 50:1007-1023(2019)

Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium

Ming J.E., Cernetti C., Steinman R.M., Granelli-Piperno A.,

J. Mol. Cell. Immunol. 4:203-211(1989)

Marked cell-type-specific differences in glycosylation of human interleukin-6

May L.T., Shaw J.E., Khanna A.K., Zabriskie J.B., Sehgal P.B.,

Cytokine 3:204-211(1991)

Structure, stability and biological properties of a N-terminally truncated form of recombinant human interleukin-6 containing a single disulfide bond

Breton J., la Fiura A., Bertolero F., Orsini G., Valsasina B., Ziliotto R., de Filippis V., Polverino de Laureto P., Fontana A.,

Eur. J. Biochem. 227:573-581(1995)

Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor

Clogston C.L., Boone T.C., Crandall B.C., Mendiaz E.A., Lu H.S.,

Arch. Biochem. Biophys. 272:144-151(1989)

Evidence for the importance of a positive charge and an alpha-helical structure of the C-terminus for biological activity of human IL-6

Luetticken C., Kruettgen A., Moeller C., Heinrich P.C., Rose-John S.,

FEBS Lett. 282:265-267(1991)

Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6

Steensberg A., van Hall G., Osada T., Sacchetti M., Saltin B., Klarlund Pedersen B.,

J. Physiol. (Lond.) 529:237-242(2000)

Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis

Nakahara H., Song J., Sugimoto M., Hagihara K., Kishimoto T., Yoshizaki K., Nishimoto N.,

Arthritis Rheum. 48:1521-1529(2003)

IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin

Nemeth E., Rivera S., Gabayan V., Keller C., Taudorf S., Pedersen B.K., Ganz T.,

J. Clin. Invest. 113:1271-1276(2004)

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