Thymus

[pjoshea13]

4 months ago in "Coronavirus & PCa" [1], I wrote:

"... removal of {testosterone} causes the involuted thymus to regenerate. That should have a positive effect on immune response."

From 7 months ago in "The Thymus." [2], I quoted from Wikipedia:

"T cells develop in the thymus & are central to the immune response. At puberty, the thymus "begins to decrease in size and activity in a process called thymic involution."

"The atrophy is due to the increased circulating level of sex hormones, and chemical or physical castration of an adult results in the thymus increasing in size and activity."" [3]

From today's New York Times "How the Coronavirus Short-Circuits the Immune System" by Gina Kolata [4]:

"Children have highly active thymus glands, the source of new T cells. That may allow them to stay ahead of the virus, making new T cells faster than the virus can destroy them. In older adults, the thymus does not function as well." {an understatement}

"One of the most striking aberrations in Covid-19 patients, the investigators found, was a marked increase in levels of a molecule called IP10, which sends T cells to areas of the body where they are needed."

"Ordinarily, IP10 levels are only briefly elevated while T cells are dispatched. But in Covid-19 patients — as was the case in patients with SARS and MERS, also caused by coronaviruses — IP10 levels go up and stay up."

"The result is that the body may be signaling T cells almost at random, confusing the immune response. Some T cells are prepared to destroy the viruses but seem undermined, behaving aberrantly. Many T cells apparently die, and so the body’s reserves are depleted — particularly in those over age 40, in whom the thymus gland, the organ that generates new T cells, has become less efficient." {again, an uderstatement}

***

If William Shakespeare had written As You Like It today, we would have the 8 stages of man. The additional stage being the ADT stage, where we are sent back to a childhood state - sans testosterone, sans libido, but with a functional thymus. The good news is that men on ADT should respond well to vaccines for influenza, pneumonia, shingles ... & eventually Covid 19.

The bad news for men with Covid 19 treated with ADT is that the regeneration of the thymus takes time.

-Patrick

[1] healthunlocked.com/advanced...

[2] healthunlocked.com/advanced....

[3] en.wikipedia.org/wiki/Thymus

[4] nytimes.com/2020/06/26/heal...

[Hidden]

This is my personal experience with ADT. My WBC count went way down. To the point that my doctors were concerned and were discussing stopping all therapies until they recovered. Also, my muscle mass decreased significantly to the point that I only had what appeared to be essential muscle. I was very weak and was losing my appetite.

I doubt that a larger thymus gland would have made up for a 50%+ decrease in WBC count.

Again, only my personal experience.

[noahware]

"The atrophy is due to the increased circulating level of sex hormones"

But as we age, it has to be more complex than that, because atrophy continues even with the DECREASE in circulating level of sex hormones that come with old age. It does appear (again) that in some respects having NO testosterone is better than LOW testosterone.

And of course the bad news for men with Covid 19 treated with ADT is that it is a mixed blessing... the regeneration of the thymus (blessing) comes along with the (curses of) lost muscle mass, lost bone density, metabolic changes, etc.

I wonder: would just blocking AR activity (with an antiandrogen), rather than eliminating T production, have similar effects of thymus regeneration?

Also wonder if this info makes ADT a bit more attractive in some cases, relative to radiation and/or chemo, both of which I gather can have negative impacts on the thymus.

[Graham49]

Patrick, I wonder if a benefit of BAT is that you get a bit of a thymus with the extra T cells in between having some testosterone?

[pjoshea13 in reply to Graham49]

Perhaps we will see a Johns Hopkins study of BAT patients & Covid 19 from that perspective? LOL

-Patrick

[immunity1]

Yes the whole issue of thymic involution after puberty and the fact that castration (surgical and chemical), at least in lab animals, appear to reverse this is interesting. It fits in with the observation that castrated farm animals appear to be more resistant to certain common diseases (parasitism). Still as adults we have plenty of T cells (albeit less, as we age) generated and 'educated' outside of the thymus which we rely on for defence. The title of a good 2020 reference follows: It is a bit of a mouthful

Gender Disparity Impacts on Thymus Aging and LHRH Receptor Antagonist-Induced Thymic Reconstitution Following Chemotherapeutic Damage

[pjoshea13 in reply to immunity1]

Here is the Abstract: ...-Patrick

"One of the main consequences of thymus aging is the decrease in naïve T cell output. This condition accelerates at the onset of puberty, and presents as a major clinical complication for cancer patients who require cytoablative therapy. Specifically, the extensive use of chemotherapeutics, such as cyclophosphamide, in such treatments damage thymic structure and eliminate the existing naïve T cell repertoire. The resulting immunodeficiency can lead to increased incidence of opportunistic infections, tumor growth relapse and/or autoimmune diseases, particularly in older patients. Thus, strategies aimed at rejuvenating the aged thymus following chemotherapeutic damage are required. Previous studies have revealed that sex hormone deprivation in male mice is capable of regenerating the thymic microenvironment following chemotherapy treatment, however, further investigation is crucial to identify gender-based differences, and the molecular mechanisms involved during thymus regeneration. Through phenotypic analyzes, we identified gender-specific alterations in thymocytes and thymic epithelial cell (TEC) subsets from the onset of puberty. By middle-age, females presented with a higher number of thymocytes in comparison to males, yet a decrease in their Aire+ medullary TEC/thymocyte ratio was observed. This reduction could be associated with an increased risk of autoimmune disease in middle-aged women. Given the concurrent increase in female Aire+ cTEC/thymocyte ratio, we proposed that there may be an impediment in Aire+ mTEChi differentiation, and Aire+ cTEChi as its upstream precursor. The regenerative effects of LHRH receptor antagonist, degarelix, on TEC subsets was also less pronounced in middle-aged females compared to males, possibly due to slower progression of thymic involution in the former, which presented with greater TEChi proportions. Furthermore, following cyclophosphamide treatment, degarelix enhanced thymocyte and mature TEC subset recovery, with faster recovery kinetics observed in females. These events were found to involve both reactivation and proliferation of thymic epithelial progenitor cells. Taken together, the findings from this study portray a relationship between gender disparity and thymus aging, and highlight the potential benefits of LHRH receptor antagonist treatment for thymic regeneration. Further research is required, however, to determine how gender may impact on the mechanisms underpinning these events."

ncbi.nlm.nih.gov/pmc/articl...

Front Immunol. 2020; 11: 302.

Published online 2020 Mar 3. doi: 10.3389/fimmu.2020.00302

PMCID: PMC7062683

PMID: 32194555

Gender Disparity Impacts on Thymus Aging and LHRH Receptor Antagonist-Induced Thymic Reconstitution Following Chemotherapeutic Damage

Michael Ly Hun,1,† Kahlia Wong,1,† Josephine Rahma Gunawan,1,† Abdulaziz Alsharif,1,† Kylie Quinn,2 and Ann P. Chidgey1,*

Author information Article notes Copyright and License information Disclaimer

1Thymus Development, Ageing and T Cell Regeneration Laboratory, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University Clayton, Melbourne, VIC, Australia

2Quinn Laboratory, Translational Immunology and Nanotechnology Research Program, School of Health and Biomedical Research, RMIT University, Melbourne, VIC, Australia

Edited by: Avinash Bhandoola, National Institutes of Health (NIH), United States

Reviewed by: Claude Perreault, Université de Montréal, Canada; Graham Anderson, University of Birmingham, United Kingdom

*Correspondence: Ann P. Chidgey [e-mail]

This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology

†These authors have contributed equally to this work

Full text:

frontiersin.org/articles/10...

[immunity1]

Thank you. I have read the paper and as I said it is a bit of a mouthfull. R