IL-6

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Ligands
IL-6 (Human)

GtoPdb Ligand ID: 4998

Synonyms: B-cell stimulatory factor 2 | CTL differentiation factor | hybridoma growth factor | interferon β2 | interleukin-6

Compound class: Endogenous peptide in human, mouse or rat

Comment: IL-6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. It is the originating member of a family of related cytokines that include IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine factor 1/B-cell stimulating factor 3 (NNT-1), neuropoietin (NPN), IL-27, and IL-31 [14]. IL-6 is produced by T and B cells, macrophages, dendritic cells, and non-immune cells such as fibroblasts, endothelial cells, glial cells, keratinocytes, and placental syncytio- and extravillous trophoblasts.
The receptors for these cytokines (except IL-31) share a common signal transducing subunit gp130 (IL6ST).
IL-6 is a critical regulator of the immune system and has been widely implicated in autoimmune disease, infection responses and in the regulation of metabolic, regenerative, and neural processes.

Species: Human

View interactive charts of activity data across species

References
1. Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS, Rajagopal S, Pai AR, Kutty S. (2020) Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper. Front Immunol, 11: 1648. DOI: 10.3389/fimmu.2020.01648. eCollection 2020 [PMID:32754159]
2. Chen Y, Gardner D, Knight DM, Lark MW, Liang B, Shealy DJ, Song X-yR, Stojanovic-Susulic V, Sweet RW, Tam SH et al.. (2009) Anti-il-6 antibodies, compositions, methods and uses. Patent number: US7560112. Assignee: Applied Molecular Evolution, Inc., Centocor Ortho Biotech Inc.. Priority date: 29/04/2005. Publication date: 14/07/2009.
3. Engler H, Brendt P, Wischermann J, Wegner A, Röhling R, Schoemberg T, Meyer U, Gold R, Peters J, Benson S et al.. (2017) Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms. Mol Psychiatry, 22 (10): 1448-1454. [PMID:28138158]
4. Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M et al.. (2011) Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet, 378 (9795): 1006-14. [PMID:21907864]
5. Finch DK, Sleeman MA, Moisan J, Ferraro F, Botterell S, Campbell J, Cochrane D, Cruwys S, England E, Lane S et al.. (2011) Whole-molecule antibody engineering: generation of a high-affinity anti-IL-6 antibody with extended pharmacokinetics. J Mol Biol, 411 (4): 791-807. [PMID:21723291]
6. Garbers C, Heink S, Korn T, Rose-John S. (2018) Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov, 17 (6): 395-412. [PMID:29725131]
7. Garcia-Martinez L, Jensen AEC, Olson K, Dutzar B, Ojala E, Kovacevich B, Latham J, Smith JTL. (2011) Nucleic acids encoding antibodies to IL-6, and recombinant production of anti-IL-6 antibodies. Patent number: US8062864. Assignee: Alderbio Holdings Llc. Priority date: 21/05/2007. Publication date: 22/11/2011.
8. Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, Bryson J, Duncan B, Zhu W, Pitzalis C et al.. (2014) Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis, 73 (9): 1607-15. [PMID:24641941]
9. Giles-Komar J, Knight D, Peritt D, Trikha M. (2007) Anti-IL-6 antibodies, compositions, methods and uses. Patent number: US7291721. Assignee: Centocor, Inc.. Priority date: 14/11/2001. Publication date: 06/11/2007.
10. Hu B, Huang S, Yin L. (2021) The cytokine storm and COVID-19. J Med Virol, 93 (1): 250-256. [PMID:32592501]
11. Morjaria JB, Babu KS, Vijayanand P, Chauhan AJ, Davies DE, Holgate ST. (2011) Sputum IL-6 concentrations in severe asthma and its relationship with FEV1. Thorax, 66 (6): 537. [PMID:20880874]
12. Rose-John S, Conaris Research Institute AG. (2001) Fusion proteins comprising two soluble gp130 molecules. Patent number: EP1148065. Assignee: Conaris Research Institute AG. Priority date: 21/04/2000. Publication date: 24/10/2001.
13. Rose-John S, Hipp E, Lenz D, Legrés LG, Korr H, Hirano T, Kishimoto T, Heinrich PC. (1991) Structural and functional studies on the human interleukin-6 receptor. Binding, cross-linking, internalization, and degradation of interleukin-6 by fibroblasts transfected with human interleukin-6-receptor cDNA. J Biol Chem, 266 (6): 3841-6. [PMID:1995637]
14. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta, 1813 (5): 878-88. [PMID:21296109]
15. Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A, Popplewell A, Adams R, Baker T, Rapecki S et al.. (2014) Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. MAbs, 6 (3): 774-82. [PMID:24670876]
16. Sun Y, Wang D, Salvadore G, Hsu B, Curran M, Casper C, Vermeulen J, Kent JM, Singh J, Drevets WC et al.. (2017) The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anhedonia in patients with rheumatoid arthritis and multicentric Castleman's disease. Brain Behav Immun, 66: 156-164. [PMID:28676350]
17. Takeuchi T, Tanaka Y, Yamanaka H, Amano K, Nagamine R, Park W, Shiozawa K, Tsukano M, Wei JC, Shao J et al.. (2016) Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial. Mod Rheumatol, 26 (1): 15-23. [PMID:26358841]
18. Uddin M, Lau LC, Seumois G, Vijayanand P, Staples KJ, Bagmane D, Cornelius V, Dorinsky P, Davies DE, Djukanović R. (2013) EGF-induced bronchial epithelial cells drive neutrophil chemotactic and anti-apoptotic activity in asthma. PLoS ONE, 8 (9): e72502. [PMID:24039773]
19. World Health Organization. Therapeutics and COVID-19: living guideline. Accessed on 08/07/2021. Modified on 08/07/2021. www.who.int, https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.2
20. Yokoyama A, Kohno N, Fujino S, Hamada H, Inoue Y, Fujioka S, Ishida S, Hiwada K. (1995) Circulating interleukin-6 levels in patients with bronchial asthma. Am J Respir Crit Care Med, 151 (5): 1354-8. [PMID:7735584]

References

1. Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS, Rajagopal S, Pai AR, Kutty S. (2020)
Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper.
Front Immunol, 11: 1648. DOI: 10.3389/fimmu.2020.01648. eCollection 2020 [PMID:32754159]

2. Chen Y, Gardner D, Knight DM, Lark MW, Liang B, Shealy DJ, Song X-yR, Stojanovic-Susulic V, Sweet RW, Tam SH et al.. (2009)
Anti-il-6 antibodies, compositions, methods and uses.
Patent number: US7560112. Assignee: Applied Molecular Evolution, Inc., Centocor Ortho Biotech Inc.. Priority date: 29/04/2005. Publication date: 14/07/2009.

3. Engler H, Brendt P, Wischermann J, Wegner A, Röhling R, Schoemberg T, Meyer U, Gold R, Peters J, Benson S et al.. (2017)
Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms.
Mol Psychiatry, 22 (10): 1448-1454. [PMID:28138158]

4. Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M et al.. (2011)
Identification of IL6R and chromosome 11q13.5 as risk loci for asthma.
Lancet, 378 (9795): 1006-14. [PMID:21907864]

5. Finch DK, Sleeman MA, Moisan J, Ferraro F, Botterell S, Campbell J, Cochrane D, Cruwys S, England E, Lane S et al.. (2011)
Whole-molecule antibody engineering: generation of a high-affinity anti-IL-6 antibody with extended pharmacokinetics.
J Mol Biol, 411 (4): 791-807. [PMID:21723291]

6. Garbers C, Heink S, Korn T, Rose-John S. (2018)
Interleukin-6: designing specific therapeutics for a complex cytokine.
Nat Rev Drug Discov, 17 (6): 395-412. [PMID:29725131]

7. Garcia-Martinez L, Jensen AEC, Olson K, Dutzar B, Ojala E, Kovacevich B, Latham J, Smith JTL. (2011)
Nucleic acids encoding antibodies to IL-6, and recombinant production of anti-IL-6 antibodies.
Patent number: US8062864. Assignee: Alderbio Holdings Llc. Priority date: 21/05/2007. Publication date: 22/11/2011.

8. Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, Bryson J, Duncan B, Zhu W, Pitzalis C et al.. (2014)
Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study.
Ann Rheum Dis, 73 (9): 1607-15. [PMID:24641941]

9. Giles-Komar J, Knight D, Peritt D, Trikha M. (2007)
Anti-IL-6 antibodies, compositions, methods and uses.
Patent number: US7291721. Assignee: Centocor, Inc.. Priority date: 14/11/2001. Publication date: 06/11/2007.

10. Hu B, Huang S, Yin L. (2021)
The cytokine storm and COVID-19.
J Med Virol, 93 (1): 250-256. [PMID:32592501]

11. Morjaria JB, Babu KS, Vijayanand P, Chauhan AJ, Davies DE, Holgate ST. (2011)
Sputum IL-6 concentrations in severe asthma and its relationship with FEV1.
Thorax, 66 (6): 537. [PMID:20880874]

12. Rose-John S, Conaris Research Institute AG. (2001)
Fusion proteins comprising two soluble gp130 molecules.
Patent number: EP1148065. Assignee: Conaris Research Institute AG. Priority date: 21/04/2000. Publication date: 24/10/2001.

13. Rose-John S, Hipp E, Lenz D, Legrés LG, Korr H, Hirano T, Kishimoto T, Heinrich PC. (1991)
Structural and functional studies on the human interleukin-6 receptor. Binding, cross-linking, internalization, and degradation of interleukin-6 by fibroblasts transfected with human interleukin-6-receptor cDNA.
J Biol Chem, 266 (6): 3841-6. [PMID:1995637]

14. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. (2011)
The pro- and anti-inflammatory properties of the cytokine interleukin-6.
Biochim Biophys Acta, 1813 (5): 878-88. [PMID:21296109]

15. Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A, Popplewell A, Adams R, Baker T, Rapecki S et al.. (2014)
Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling.
MAbs, 6 (3): 774-82. [PMID:24670876]

16. Sun Y, Wang D, Salvadore G, Hsu B, Curran M, Casper C, Vermeulen J, Kent JM, Singh J, Drevets WC et al.. (2017)
The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anhedonia in patients with rheumatoid arthritis and multicentric Castleman's disease.
Brain Behav Immun, 66: 156-164. [PMID:28676350]

17. Takeuchi T, Tanaka Y, Yamanaka H, Amano K, Nagamine R, Park W, Shiozawa K, Tsukano M, Wei JC, Shao J et al.. (2016)
Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial.
Mod Rheumatol, 26 (1): 15-23. [PMID:26358841]

18. Uddin M, Lau LC, Seumois G, Vijayanand P, Staples KJ, Bagmane D, Cornelius V, Dorinsky P, Davies DE, Djukanović R. (2013)
EGF-induced bronchial epithelial cells drive neutrophil chemotactic and anti-apoptotic activity in asthma.
PLoS ONE, 8 (9): e72502. [PMID:24039773]

19. World Health Organization.
Therapeutics and COVID-19: living guideline.
Accessed on 08/07/2021. Modified on 08/07/2021. www.who.int, https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.2

20. Yokoyama A, Kohno N, Fujino S, Hamada H, Inoue Y, Fujioka S, Ishida S, Hiwada K. (1995)
Circulating interleukin-6 levels in patients with bronchial asthma.
Am J Respir Crit Care Med, 151 (5): 1354-8. [PMID:7735584]

IL-6

GtoPdb Ligand ID: 4998

Ligand Activity Visualisation Charts