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.
J Immunol. 2005 Jun 1;174(11):7398-402.
Wysocka, M., Montaner, L.J., Karp, C.L.
“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.”
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.”
Reversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot study.
“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?
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.”
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
“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!