The Thyroid Hormone Inactivating Type 3 Deiodinase Is Essential for Optimal Neutrophil Function: Observations From Three Species

[helvella]

OK, OK - so Deiodinase Type 3 is essential for the functioning of neutrophils. But WHY?

[Many years ago, I remember reading the idea that in certain circumstances thyroid hormone(s) would be deiodinated in order to release iodine atoms - with the iodine then being available to kill bacteria (or whatever). Seemed a neat idea but rather too fanciful. However, the marked increase in thyroxine and reverse-T3 reported here is interesting. More T4 to deliver more iodine, but deiodinated - and releasing that iodine atom - to rT3 so as to avoid increasing T3? Surely not? Feel free to tell me what an idiotic idea this is. ]

Endocrinology. 2018 Feb 1;159(2):826-835. doi: 10.1210/en.2017-00666.

The Thyroid Hormone Inactivating Type 3 Deiodinase Is Essential for Optimal Neutrophil Function: Observations From Three Species.

van der Spek AH1, Jim KK2,3, Karaczyn A4, van Beeren HC1, Ackermans MT5, Darras VM6, Vandenbroucke-Grauls CMJE3, Hernandez A4, Brouwer MC2, Fliers E1, van de Beek D2, Boelen A1.

Author information

1 Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

2 Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

3 Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands.

4 Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine.

5 Laboratory of Endocrinology, Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

6 Laboratory of Comparative Endocrinology, Department of Biology, KU Leuven, Leuven, Belgium.

Abstract

Neutrophils are essential effector cells of the innate immune system that have recently been recognized as thyroid hormone (TH) target cells. Cellular TH bioavailability is regulated by the deiodinase enzymes, which can activate or inactivate TH. We have previously shown that the TH inactivating enzyme type 3 deiodinase (D3) is present in neutrophils. Furthermore, D3 knockout (D3KO) mice show impaired bacterial killing upon infection. We hypothesized that D3 plays a role in neutrophil function during infection by actively regulating local TH availability. We measured TH concentrations in cerebrospinal fluid (CSF) from patients with bacterial meningitis and controls. Bacterial meningitis resulted in marked changes in CSF TH levels, characterized by a strong increase of thyroxine and reverse-triiodothyronine concentrations. This altered TH profile was consistent with elevated D3 activity in infiltrating neutrophils at the site of infection. D3 knockdown in zebrafish embryos with pneumococcal meningitis resulted in increased mortality and reduced neutrophil infiltration during infection. Finally, stimulated neutrophils from female D3KO mice exhibited impaired NADPH-oxidase activity, an important component of the neutrophil bacterial killing machinery. These consistent findings across experimental models strongly support a critical role for reduced intracellular TH concentrations in neutrophil function during infection, for which the TH inactivating enzyme D3 appears essential.

PMID: 29186449

PMCID: PMC5774253 [Available on 2019-02-01]

DOI: 10.1210/en.2017-00666

Free access to full paper will be available - eventually - on 01/02/2019 - for now, just the abstract:

ncbi.nlm.nih.gov/pubmed/291...

[gabkad]

Maybe this is why in very sick people thyroid hormone levels go down which seems paradoxical. But if the body is using the hormone like this, then it would make sense.

[Justiina]

Wouldn't that sort of explain why in CFS (according to article diogenes posted earlier) low iodine is often found? I mean if in CFS there is often inflammation which would then increase the need of iodine and TH?

Or am I just way too far out?

[helvella Administrator in reply to Justiina]

I'd love to see that thought followed through properly.

[Justiina in reply to helvella]

Going even further and throwing this in telegraph.co.uk/science/201...

As a culprit of inflammation leading to problems : drugs -> inflammation-> need of higher TH -> lower TH -> feeling worse. If Simvastatin is usually the one making people feel rotten and muscular symptoms (common low t3 symptom) could it be this way?

Thyroxine -> SIBO -> not only poor conversion but higher need of T3 due ongoing inflammation.

Etc. Etc.

Just letting my mind wonder freely around this

[helvella Administrator in reply to Justiina]

Which effectively re-asks whether taking medicines orally is such a good idea?

(Obviously the answer will vary across the many medicines used.)

Certainly some would affect the gut however they were taken, but possibly some only have that negative impact on the gut when taken orally.

[Justiina in reply to helvella]

Exactly. There are many different type of scenarios of why and how. In the end nature beats medicine 100-0 so many ways. Certain drugs may save your life but in the end nature fights back as it's foreign substance and doesn't belong into human body. That's why it would be elementary to fix the attitude and start supporting healthy habits and use drugs only when necessary.