Anti-IL-6

Anti-interleukin-6 agents are a class of therapeutics. Interleukin 6 is a cytokine relevant to many inflammatory diseases and many cancers.[1] Hence, anti-IL6 agents have been sought.[2][3][4][5][6] In rheumatoid arthritis they can help patients unresponsive to TNF inhibitors.[7]

The first approved medication in this class, tocilizumab (Actemra), is an antibody directed against the IL6-receptor.[8] The second, siltuximab (Sylvant), is directed against IL-6 itself.[1][9]

Several agents are in clinical trials: sarilumab,[10] olokizumab (CDP6038)[11][12] elsilimomab, BMS-945429(ALD518), sirukumab (CNTO 136), and CPSI-2364 an apparent macrophage-specific inhibitor of the p38 mitogen-activated protein kinase pathway.[13] ALX-0061.[7]:Table1

e.g. for rheumatoid arthritis : clazakizumab, olokizumab, sarilumab and sirukumab have all reported encouraging phase 2 results.[7] Sirukumab is in multiple phase 3 trials.[7]:Table1

Agents in pre-clinical development include ARGX-109,[14][15] FE301,[1] FM101[16]

Exercise induced IL-6 may be beneficial

New research has found IL-6 to be an anti-inflammatory cytokine with multiple beneficial effects when released by contracting muscle as a myokine. IL-6 had previously been classified as a proinflammatory cytokine. Therefore, it was first thought that the exercise-induced IL-6 response was related to muscle damage.[17] However, it has become evident that eccentric exercises are not associated with a larger increase in plasma IL-6 than exercise involving concentric “nondamaging” muscle contractions. This finding demonstrates that muscle damage is not required to provoke an increase in plasma IL-6 during exercise. In fact, eccentric exercise may result in a delayed peak and a much slower decrease of plasma IL-6 during recovery.[18] Anti-IL-6 therapies should therefore take into consideration the (beneficial) anti-inflammatory effects of myokines generally, including the now-established multiple benefits of muscle-derived Interleukin 6.[18]

Food and diet

It has been reported that lunasin, a soy peptide, reduces inflammation by reducing interleukin 6 and may help in leukemia.[19]

Luteolin reduces IL-6 production in some neurons.[20]

References

  1. 1 2 3 Jones SA, Scheller J, Rose-John S (2011). "Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling". J. Clin. Invest. 121 (9): 3375–83. doi:10.1172/JCI57158. PMC 3163962. PMID 21881215.
  2. ↑ Barton BE (August 2005). "Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative diseases and paraneoplastic syndromes". Expert Opin. Ther. Targets 9 (4): 737–52. doi:10.1517/14728222.9.4.737. PMID 16083340.
  3. ↑ Smolen JS, Maini RN (2006). "Interleukin-6: a new therapeutic target". Arthritis Research & Therapy. 8 Suppl 2: S5. doi:10.1186/ar1969. PMC 3226077. PMID 16899109.
  4. ↑ Stein and Sutherland (1998). "IL-6 as a drug discovery target". Drug Discovery Today 3 (5): 202–213. doi:10.1016/S1359-6446(97)01164-1.
  5. ↑ "Interleukin-6 - new target in the battle against Ras-induced cancers". 2007.
  6. ↑ "Interleukin 6 as a therapeutic target in systemic-onset juvenile idiopathic arthritis". 2003.
  7. 1 2 3 4 Tanaka & Mola (2014). "IL-6 targeting compared to TNF targeting in rheumatoid arthritis: studies of olokizumab, sarilumab and sirukumab".
  8. ↑ Schoels MM, van der Heijde D, Breedveld FC, et al. (2013). "Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement". Ann. Rheum. Dis. 72 (4): 583–9. doi:10.1136/annrheumdis-2012-202470. PMC 3595140. PMID 23144446.
  9. ↑ http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125496s000lbl.pdf
  10. ↑ http://www.clinicaltrials.gov/ct2/results?term=sarilumab
  11. ↑ "UCB Announces Start Of Phase I Study For Antibody Drug Candidate CDP6038". 2 Dec 2008.
  12. ↑ http://www.pharmatimes.com/article/12-09-28/UCB_s_RA_drug_does_not_overly_impress_in_Phase_II.aspx
  13. ↑ PMID: 23598944
  14. ↑ "ArGEN-X Wins €1.5M IWT Grant to Progress Camelid-Derived Human Antibody Pipeline". 27 Sep 2010.
  15. ↑ http://www.prnewswire.com/news-releases/ruiyi-formerly-anaphore-and-argen-x-announce-exclusive-worldwide-license-agreement-for-argx-109-a-novel-anti-il-6-antibody-172634271.html
  16. ↑ "Formatech to Donate Services to Formulate and Fill Femta Pharmaceuticals’ FM101 Monoclonal Antibody under Its "Fillanthrop". 30 July 2010.
  17. ↑ Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, Johansen TL, MacLean DA, Pedersen BK. Exercise-induced increase in interleukin-6 is related to muscle damage. J Physiol Lond 499: 833-841, 1997.
  18. 1 2 Muscle as a secretory organ. Pedersen BK. American Physiological Society. Compr Physiol 3:1337-1362, 2013. http://www.inflammation-metabolism.dk/index.php?pageid=21&pmid=23897689
  19. ↑ http://www.foodconsumer.org/newsite/Nutrition/Supplements/soy_protein_helps_fight_cancer_and_inflammation_021220090906.html
  20. ↑ Johnson; Kelley, KW; Johnson, RW; et al. (May 2008). "Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1 — PNAS". Proceedings of the National Academy of Sciences of the United States of America 105 (21): 7534–9. doi:10.1073/pnas.0802865105. PMC 2396685. PMID 18490655.
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