Interleukin-6 (IL-6)

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.

Interleukin-6 (IL-6)

Postby admin » Sun May 17, 2020 9:37 am

© 2020 PFPC


[i]"There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications."

(Russell et al., 2020)

Russell B, Moss C, George G, Santaolalla A, Cope A, Papa S, Van Hemelrijck M - "Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence" Ecancermedicalscience 14:1022 (2020)
doi: 10.3332/ecancer.2020.1022. PMID: 32256705; PMCID: PMC7105343

"Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases."

(Zhu et al, 2020)

Zhu Z, Cai T, Fan L, Lou K, Hua X, Huang Z, Gao G - "Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019" Int J Infect Dis 95:332-339 (2020). doi: 10.1016/j.ijid.2020.04.041. Epub ahead of print. PMID: 32334118; PMCID: PMC7195003.


Gao Y, Li T, Han M, Li X, Wu D, Xu Y, Zhu Y, Liu Y, Wang X, Wang L - "Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19" J Med Virol (2020) doi: 10.1002/jmv.25770. Epub ahead of print. PMID: 32181911.


Malko NV, Besvushko EV - "Dynamics of immunological features of oral liquid in children with chronic catarrhal gingivitis living on polluted territories with fluoride and iodine deficiency" Stomatologiia (Mosk) 96(2):51-54 (2017) Russian. doi: 10.17116/stomat201796251-54. PMID: 28514348.
(-> increase in pro-inflammatory cytokine IL-6 with the decrease of anti-inflammatory cytokine IL-4)

Bezvushko EV, Malko NV - 'Cytokine dysregulation in children with chronic catarrhal gingivitis living in polluted areas with fluoride and iodine deficiency". Stomatologiia (Mosk) 96(4):48-51(2017) Russian. doi: 10.17116/stomat201796448-51. PMID: 28858281.

"A marked increase in the mRNA level for IL-6 was observed already 2 h after exposure to 5 mM NaF, and presumably is a prerequisite for the subsequent increase of IL-6. The fluoride-induced effects on IL-6 and IL-8 release were strongly reduced by pretreatment with deferoxamine (an Al3+-chelator), and enhanced by addition of Al3+. This indicates that an AlF4-- complex, a known activator of GTP-binding proteins, is involved in fluoride-induced IL-6 and IL-8 responses in A549 cells."

(Refsnes et al., 1999)

Refsnes M, Becher R, Lâg M, Skuland T, Schwarze PE - "Fluoride-induced interleukin-6 and interleukin-8 synthesis in human epithelial lung cells" Hum Exp Toxicol 18(11):645-52 (1999) doi: 10.1191/096032799678839572. PMID: 10602388.

G q/11:

"We conclude that extracellular acidification stimulates IL-6 production and Ca(2+) mobilization through proton-sensing OGR1 receptors/G(q/11) proteins in human airway smooth muscle cells."

(Ichimonji et al., 2010)

Ichimonji I, Tomura H, Mogi C, Sato K, Aoki H, Hisada T, Dobashi K, Ishizuka T, Mori M, Okajima F - "Extracellular acidification stimulates IL-6 production and Ca(2+) mobilization through proton-sensing OGR1 receptors in human airway smooth muscle cells" Am J Physiol Lung Cell Mol Physiol 299(4):L567-77 (2010)
doi: 10.1152/ajplung.00415.2009. Epub 2010 Jul 23. PMID: 20656891

"These results suggest that UTP-induced IL-6 production is in part mediated via phosphorylation of ERK through G(q/11)/IP(3)/[Ca(2+)](i) and transactivation of the EGF receptor...."

(Kobayashi et al., 2006)

Kobayashi D, Ohkubo S, Nakahata N. - "Contribution of extracellular signal-regulated kinase to UTP-induced interleukin-6 biosynthesis in HaCaT keratinocytes" J Pharmacol Sci 102(4):368-76 (2006)
doi: 10.1254/jphs.fp0060669. Epub 2006 Nov 28. PMID: 17130674

Abbott KL, Loss JR 2nd, Robida AM, Murphy TJ - "Evidence that Galpha(q)-coupled receptor-induced interleukin-6 mRNA in vascular smooth muscle cells involves the nuclear factor of activated T cells" Mol Pharmacol 58(5):946-53 (2000) doi: 10.1124/mol.58.5.946. PMID: 11040041

Others - Fluoride:

Refsnes M, Schwarze PE, Holme JA, Låg M - "Fluoride-induced apoptosis in human epithelial lung cells (A549 cells): role of different G protein-linked signal systems" Hum Exp Toxicol 22(3):111-23 (2003) doi: 10.1191/0960327103ht322oa PMID: 12723891

Refsnes M, Thrane EV, Låg M, Thoresen GH, Schwarze PE - "Mechanisms in fluoride-induced interleukin-8 synthesis in human lung epithelial cells" Toxicology 167(2):145-58 (2001) doi: 10.1016/s0300-483x(01)00448-6 PMID: 11567778

Refsnes M, Skuland T, Schwarze PE, Øvrevik J, Låg M - "Fluoride-induced IL-8 release in human epithelial lung cells: relationship to EGF-receptor-, SRC- and MAP-kinase activation" Toxicol Appl Pharmacol 227(1):56-67 (2008) doi: 10.1016/j.taap.2007.09.022. Epub 2007 Oct 3. PMID: 17996917

Ridley W, Matsuoka M - "Fluoride-induced cyclooxygenase-2 expression and prostaglandin E2 production in A549 human pulmonary epithelial cells" Toxicol Lett 188(3):180-5 (2009) doi: 10.1016/j.toxlet.2009.04.007. Epub 2009 Apr 17.
PMID: 19376214

Kawase T, Ishikawa I, Orikasa M, Suzuki A - "Aluminum enhances the stimulatory effect of NaF on prostaglandin E2 synthesis in a clonal osteoblast-like cell line, MOB 3-4, in vitro" J Biochem 106(1):8-10 (1989)
doi: 10.1093/oxfordjournals.jbchem.a122824.
PMID: 2777755


Contreras-Jurado C, Alonso-Merino E, Saiz-Ladera C, Valiño AJ, Regadera J, Alemany S, Aranda A - "The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia" Sci Rep 6:30990 (2016)
doi: 10.1038/srep30990. PMID: 27484112; PMCID: PMC4971531.

Hodkinson CF, Simpson EE, Beattie JH, O'Connor JM, Campbell DJ, Strain JJ, Wallace JM - "Preliminary evidence of immune function modulation by thyroid hormones in healthy men and women aged 55-70 years" J Endocrinol 202(1):55-63 (2009) doi: 10.1677/JOE-08-0488. Epub 2009 Apr 27. PubMed PMID:19398496 ... 2/1/55.xml

Bartalena L, Brogioni S, Grasso L, Rago T, Vitti P, Pinchera A, Martino E - "Interleukin-6: a marker of thyroid-destructive processes?" J Clin Endocrinol Metab. 79(5):1424-7 (1994) doi: 10.1210/jcem.79.5.7962338. PMID: 7962338 ... 24/2649325
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