IL-2

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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IL-2

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IL-2R
© 2020 PFPC

COVID-19
"Early reports have demonstrated severely elevated levels of inflammatory biomarkers and cytokines, including IL-6, C-reactive
protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-2R and ferritin (112)."
(in Atri et al., 2020)

Atri D, Siddiqi HK, Lang J, Nauffal V, Morrow DA, Bohula EA - "COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies" JACC Basic Transl Sci Apr 10 (2020) doi: 10.1016/j.jacbts.2020.04.002. Epub ahead of print. PMID: 32292848; PMCID: PMC7151394.
https://www.ncbi.nlm.nih.gov/pmc/articl ... f/main.pdf

Fluoride:

NOTE: There are dose and time-dependent effects. Low amounts of fluoride produce elevated levels of IL-2, while high doses inhibit IL-2 (Hosokawa et al., 2015; Afolabi et al., 2013; Guo et al., 2017; Zhang et al., 2020).

Yubing Deng, Hengmin Cui, Xi Peng, Jing Fang, Zhicai Zuo, Junliang Deng, Qin Luoa - "High dietary fluorine alteration of serum cytokine and immunoglobulin in broilers" Fluoride 46(3):118-127 (2013)
http://www.fluorideresearch.org/463/fil ... 127_pq.pdf

Hosokawa M, Tsunoda M, Liu Y, Nakano K, Itai K, Tsunoda H, Yokoyama K, Aizawab Y - "The immunotoxic effects of fluoride on mice after subacute administration by evaluating cytokine mRNA expression in splenocytes" Fluoride 48(4)329-337 (2015)
http://www.fluorideresearch.org/484/fil ... 37_sfs.pdf

"... interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05)."

(Afolabi et al., 2013)

Afolabi OK, Oyewo EB, Adekunle AS, Adedosu OT, Adedeji AL - "Oxidative indices correlate with dyslipidemia and pro-inflammatory cytokine levels in fluoride-exposed rats" Arh Hig Rada Toksikol 64(4):521-9 (2013) doi: 10.2478/10004-1254-64-2013-2351. PMID: 24384758.
PFPC Library Link

Guo H, Kuang P, Luo Q, Cui H, Deng H, Liu H, Lu Y, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Effects of sodium fluoride on blood cellular and humoral immunity in mice" Oncotarget 8(49):85504-85515 (2017) doi: 10.18632/oncotarget.20198. PMID: 29156736; PMCID: PMC5689626.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689626/

"In summary, our study demonstrated that fluoride inhibits Hepa1-6 cell growth and results in disorders in the expression and secretion pro-inflammatory cytokines."


(Zhang et al., 2020)

Zhang Y, Zhou BH, Tan PP, Chen Y, Miao CY, Wang HW - "Key Role of Pro-inflammatory Cytokines in the Toxic Effect of Fluoride on Hepa1-6 Cells" Biol Trace Elem Res doi: 10.1007/s12011-019-01967-1 (2020) Epub ahead of print. PMID: 31983054
https://pubmed.ncbi.nlm.nih.gov/31983054/

Loftenius A, Andersson B, Butler J, Ekstrand J - "Fluoride augments the mitogenic and antigenic response of human blood lymphocytes in vitro" Caries Res. 33(2):148-55 (1999) doi: 10.1159/000016509. PMID: 9892783
https://www.karger.com/Article/Abstract/16509

Gq/11

Beadling C, Druey KM, Richter G, Kehrl JH, Smith KA - "Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes" J Immunol 162(5):2677-82 (1999) PMID: 10072511
https://pubmed.ncbi.nlm.nih.gov/10072511/

Al-Aoukaty A, Rolstad B, Maghazachi AA - "Functional coupling of NKR-P1 receptors to various heterotrimeric G proteins in rat interleukin-2-activated natural killer cells" J Biol Chem 272(50):31604-8 (1997) doi: 10.1074/jbc.272.50.31604. PMID: 9395499
https://pubmed.ncbi.nlm.nih.gov/9395499/

NOTE: Both inorganic and organic fluoride may influence Gq/11 pathways, and affect IL-2 levels.

Kovárů H, Kovaru F, Ondráčkova P, Lisá V, Fiserová A - "Effect of fluoxetine or adenosine receptor NECA agonist on G-proteins of C6 glioma cells or NK immunocytes" Neuro Endocrinol Lett 32(3):274-8 (2011) PMID: 21712787
https://pubmed.ncbi.nlm.nih.gov/21712787/

Thyroid

"We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone."

Nakanishi K, Taniguchi Y, Ohta Y - "Increased soluble interleukin 2 receptor levels in autoimmune thyroid disease" Acta Endocrinol (Copenh). 1991;125(3):253‐258 (1991) doi:10.1530/acta.0.1250253
https://pubmed.ncbi.nlm.nih.gov/1683085/

"We showed that sIL-2R was the best cytokine marker, showing very good correlation with the endocrine status of GD patients."

Komorowski J, Jankiewicz J, Robak T, Błasińska-Morawiec M, Stepień H - "Cytokines serum levels as the markers of thyroid activation in Graves' disease" Immunol Lett 60(2-3):143‐148 (1998) doi:10.1016/s0165-2478(97)00151-x
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