Potayto/Potahto: Post-Sepsis/Immunoparalysis

I learned something new this week. This little thing we like to call “chronic Lyme” that’s actually post-sepsis syndrome (according to the NIH), is also called “immunoparalysis.” And the really great thing about that is, the research goes back to at least 1980 and ties in “endotoxin tolerance,” which is what happens when your immune system is shut off by the OspA or other fungal-type antigen, and doesn’t recognize (and therefore doesn’t fight) fungal antigens any more.

CDC Officer Alan Barbour was the dude who said OspA “overwhelms” the immune system, when describing what antigenic variation in spirochetes does to humans (US Patent 6,719,983). This is a term you want to remember in case you hear it again: “overwhelmed” immune system means: “turned off.” “Turned off” is the complete opposite of an “inflammatory” or “autoimmune disease.”

Here is a handy graphic I created to further illustrate what’s going on:

 

Feel free to download and share. I do all of this with the intent that it will be shared. We all own the truth!

So, anyway, now we have a number of terms to describe this condition of an overwhelmed, or turned off, immune system. Chronic Lyme, Post-Sepsis Syndrome, Immunoparalysis…potayto, potahto.

I’ve gathered a bunch of Immunoparalysis links here, for your reading pleasure. Some even address potential treatments! I apologize for the wacky mix of fonts, as I’m doing most of my posts via mobile and can’t always change my cut-pastes.

 

Flt3 ligand treatment reverses endotoxin tolerance-related immunoparalysis.

J Immunol. 2005 Jun 1;174(11):7398-402.

Wysocka, M., Montaner, L.J., Karp, C.L.

  • Department of Dermatology, University of Pennsylvania, Philadelphia, 19104, USA. (Dermatologists? Are you kidding me? For shame, ID docs…)

“Endotoxin tolerance, the secondary blunting of a subset of microbial product-driven responses, is presumed to provide protection from pathological hyperactivation of the innate immune system during infection. However, endotoxin tolerance can itself be harmful. A significant percentage of sepsis survivors exhibit the phenotype of systemic endotoxin tolerance, a state termed immunoparalysis. Similar immune hyporeactivity, associated with an elevated risk of succumbing to bacterial superinfection, is also seen in the aftermath of major trauma, surgery, and burns. We recently demonstrated that in vivo endotoxin tolerance in murine models involves dendritic cell loss as well as alterations in the responsiveness of macrophages and remaining dendritic cells. Furthermore, the kinetics of recovery from immunoparalysis-associated inhibition of proinflammatory and immunoregulatory cytokine production directly parallels the kinetics of dendritic cell repopulation in these models. Given this, we examined whether recovery from immunoparalysis could be accelerated therapeutically with flt3 ligand, a growth factor that stimulates the differentiation and mobilization of dendritic cells. Notably, administration of flt3 ligand rapidly reverses immunoparalysis in vivo, accelerating and amplifying repopulation of tissues with proinflammatory and immunoregulatory cytokine-producing dendritic cells.”

_________________________________________________________

Pathophysiology of sepsis and recent patents on the diagnosis, treatment and prophylaxis for sepsis.

Recent Pat Inflamm Allergy Drug Discov. 2009 Jan;3(1):26-32. 

Okazaki, Y. & Matsukawa, A.

  • 1Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata, Okayama, Japan.

“More recent data indicate that most septic patients survive this stage and then subjected to an immunoparalysis phase, termed compensatory anti-inflammatory response syndrome (CARS), which is more fatal than the initial phase.”

______________________________________________________________
This work was supported by Grant No. K08HL085525 from the National Institutes of Health:
Reversibility of Immunoparalysis
Pediatric Clinics of North America, June 2008
W. Joshua Frazier, MD and Mark W. Hall, MD
 

“As the natural history of innate immune dysfunction in critical illness becomes clearer, a question arises: Is immunoparalysis simply an epiphenomenon associated with critical illness or does it represent a reversible target for intervention in hopes of improving outcomes? The answer to this question is far from clear, but several lines of evidence suggest that the latter may be true.”

____________________________________________________________

Reversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot study.

Am J Respir Crit Care Med. 2012 Nov 1;186(9):838-45. doi: 10.1164/rccm.201204-0645OC. Epub 2012 Jul 19.

http://www.ncbi.nlm.nih.gov/pubmed/22822024

“Conclusion: IFN-γ partially reverses immunoparalysis in vivo in humans. These results suggest that IFN-γ is a promising treatment option to reverse sepsis-induced immunoparalysis.”

____________________________________________________________________

Should We Be Moving From Suppression to Stimulation to Deal With Immunoparalysis in Sepsis Patients?

 

Evangelos J Giamarellos-Bourboulis

Immunotherapy. 2014;6(2):113-115. 

Unfortunately, this one is behind a membership/paywall on Medscape.

“Among them, IgM preparations are more close to the bedside. Part of the phenomenon of immunoparalysis involves exhaustion of B lymphocytes for IgM production. IgM is a polyvalent immunoglobulin that is very effective for the opsonization of microrganisms and for the blockade of bacterial endotoxins and cytokines.[5]”

How to Identify Systemic Sepsis-Induced Immunoparalysis

Guillaume Monneret Advances in Sepsis 2005;4(2)42–9. 

Flow Cytometry Unit, Immunology Laboratory, Lyon-Sud University Hospital, Pierre-Bénite, France 

http://www.ucdenver.edu/academics/colleges/medicalschool/departments/medicine/intmed/imrp/CURRICULUM/Documents/AB1.Sepsis_Pathophysiology%2814%29.pdf

“The body develops compensatory mechanisms to prevent systemic inflammation in response to stress and
injury. As overwhelming inflammation is rapidly lethal, these mechanisms have a protective effect during
the first few hours after injury. However, they become deleterious as nearly all immune functions are
compromised. The term “immunoparalysis” describes the global incapacity of the body to mount any kind
of immune response; the extent of immunoparalysis is thought to correlate with life-threatening
secondary infections and mortality. The hypoimmune state might require proinflammatory therapies to
enhance immune function, but establishing the presence of immunodepression is crucial when
considering such an approach. This article discusses methods for diagnosing immunoparalysis, in
particular measurements of circulating monocyte human leukocyte antigen type DR expression and
plasma interleukin-10. “

You can also go on PubMed and search the term Immunoparalysis or any combination of terms you see here. Try it–it’s fun! 

 

Now, I just want to take you back to Anthony Fauci, head of the NIAID, for a sec. (For background, see my Tony The Tiger post.)


Amazingly, if one searches the patent database, one would find a Fauci-owned patent for the treatment of immune suppression outcomes of bacterial, viral, and fungal infections:
http://patft.uspto.gov/netacgi/nph-Pars … /5,696,079

FIELD OF THE INVENTION
The present invention pertains to a method for activating the immune system of a patient by intermittently administering interleukin-2 (IL-2) to that patient. Such administration of IL-2 can optionally be combined with other therapies, such as anti-retroviral, anti-bacterial or anti-fungal therapies, suitable for treatment of the patient’s condition. This invention also relates to an approach to gene therapy that entails administering IL-2 to a patient so as to facilitate in situ lymphocyte transduction by a retroviral vector also administered to the patient. 

 
Fauci has patented a treatment for the immune suppression outcomes of Lyme disease, but he simultaneously denies the existence of those outcomes. Somebody show him the 114 Immunoparalysis reports in PubMed, please. He might like to know that his own agency is involved in some of the research. 
 


Categories: Immunosuppression Diseases, Lyme Disease

Tags: , , ,

13 replies

  1. So Beaux, here’s my question…..what to actually DO for a person with immunoparalysis?? And since you say it is the opposite of inflammation would a person showing inflammation in their labs be someone who is NOT in immunoparalysis?

    Like

    • There have been positive results in European trials with Rituximab (b-cell depleter) for CFS. I’ve also seen it studied for lupus. (We know from Yale that lupus is a Lyme outcome.) This makes sense when you look at the data in the Occam’s Razor post re incompetent b-cells. I’m not making a treatment recommendation; just regurgitating what the science says.

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  2. Thank you, very interesting read. I’m wondering if breast implants don’t also cause the same type immune suppression.

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  3. This one comes on top of the banners i choose out in my post on Cryme Disease; Connect the dots.

    You are brilliant – and thanks for making these banners.

    http://www.crymedisease.com/#!connect-the-dots/pzx1o

    Go SASH

    Liked by 1 person

  4. I happened to run into “post-sepsis syndrome” this week while doing some research in my spare time. Holy cow! Yet another major, obvious connection to our predicament that’s being completely misrepresented and misinterpreted. I was so fascinated by what I was reading (there is even a nonprofit pt. org dedicated to victims of it) that I made some time today to dig some more. And lookie here! I ran smack-dab into your blog post from March on this very topic! So you’ve discovered the same, Beaux — Great minds, SOS, etc, etc. LOL.

    Thanks especially for this one and for digging up the research. Just WOW. And did ya see that there is now a “post ebola syndrome,” too? Seems to me that the powers that be love to dub active infections as post-anything (anything BUT in the here and now). How neat and tidy of them.

    Keep up the outstanding work! -C

    Like

  5. good blog, thank you very much !

    Liked by 1 person

  6. Reblogged this on The Other Side Of The Stretcher and commented:
    Another informational blog from Bad Lyme Attitude Blog!
    Looks good!

    Liked by 1 person

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