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Cytokine storm or immunopathology

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Cytokine storm or immunopathology

Postby cave76 » Wed 3 Oct 2007 20:22

From that great medical reference site, Wikipedia. :D

http://en.wikipedia.org/wiki/Cytokine_storm

Hey, it's easy to understand. LOL

Cytokine storm
From Wikipedia, the free encyclopedia

A cytokine storm is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.

The primary symptoms of a cytokine storm are a high fever, swelling and redness, extreme fatigue, and nausea.

When the immune system is fighting pathogens, cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines. Normally this feedback loop is kept in check by the body. However, in some instances, the reaction becomes uncontrolled, and too many immune cells are activated in a single place. The precise reason for this is not entirely understood, but may be caused by an exaggerated response when the immune system encounters a new and highly pathogenic invader. Cytokine storms have potential to do significant damage to body tissues and organs. If a cytokine storm occurs in the lungs, for example, fluids and immune cells such as macrophages may accumulate and eventually block off the airways, potentially resulting in death.

The cytokine storm (hypercytokinemia) is the systemic expression of a healthy and vigorous immune system resulting in the release of more than 150 inflammatory mediators (cytokines, oxygen free radicals, and coagulation factors). Both pro-inflammatory cytokines (such as Tumor necrosis factor-alpha, Interleukin-1, and Interleukin-6) and anti-inflammatory cytokines (such as interleukin 10, and interleukin 1 receptor antagonist) are elevated in the serum of patients experiencing a cytokine storm.

Cytokine storms can occur in a number of infectious and non-infectious diseases including graft versus host disease (GVHD), adult respiratory distress syndrome (ARDS), sepsis, avian influenza, smallpox, and systemic inflammatory response syndrome (SIRS).[1]

The first reference to the term "cytokine storm" in the published medical literature appears to be by Ferrara et al in GVHD, in February 1993.

********************

Then another person's take (not mine, but it's interesting)

I'll ignore the references to the Marshall Protocol and Benicar as not pertinent to this forum.

Immunopathology


A new medical term, immunopathology, is being used to replace Jarisch-Herxheimer among the scientific community. Immunopathology refers to a branch of medicine that deals with the study of how the body fights off disease and the study of immunodeficiency diseases. Although the Herxheimer reaction and immunopathology have similar meanings, there is an important difference. Therefore, in order to be taken seriously by researchers who appreciate the difference, we must discard the use of Herxheimer as too vague and begin to use 'immunopathology' because its meaning is more accurate and acceptable.

According to wikipedia, "immunopathology refers to diseases of or caused by the immune system, such as autoimmune (hypersensitivity) diseases such as type I diabetes, allergies. In this sense 'immunopathogenic' diseases are those which infect the immune system such as HIV, and leukemias.

Immunopathology is used to denote malaise (disease) caused by the immune system during normal function. As the intraphagocytic bacteria are killed, the cells they lived in also die (apoptosis), and as the immune system tries to clear them up, patients experience malaise. Malaise comes not just from the 'cytokine storm', but also from the changes in CBC (Complete Blood Count). This explains the malaise we see as Benicar starts to kick in and activate the VDR and the reaction to the MP antibiotics, both direct and indirect from bacteria which have been killed.

The term immunopathology provides a far more detailed description of what is happening in, and during recovery from, chronic Th1 inflammatory diseases than the Herxheimer response which does not describe the collateral effects on the body and is commonly thought to occur only during acute bacterial illnesses.

Immunopathology means all the pathological changes, hormonal, endocrine, cell death and CBC changes, which occur as the immune system is doing its job and this is a critical distinction.

.....................................................................................

Jarisch-Herxheimer is correctly used only when describing an acute immunopathologic reaction such as was first seen in syphilis and is often noted with the initial treatment of acute Lyme disease. If doctors are familiar with the Herx reaction, it is in the context of treatment of an acute infection.

The Herxheimer reaction does not describe all the immunopathologic changes seen with continued effective treatment of chronic inflammation due to intracellular bacteria.

It is important for patients to differentiate between symptoms due to the initial profound hormonal changes when the Benicar blockade is put in place, symptoms provoked by stimulation due to sun exposure and symptoms due to bacterial kill because awareness leads to better management of symptoms during treatment.

Hormonal, endocrine, cell death and CBC changes, manifested in symptoms, will take place as long as CWD bacteria are being killed. Scientists understand these effects of the immune system reaction as immunopathology, a term which encompasses the total phenomenon of this continued response to long-term treatment.

Truncated
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Re: Cytokine storm or immunopathology

Postby LymeEnigma » Sun 28 Oct 2007 20:17

Cytokine storm sounds very much like the attacks I used to get from the babesia ... vomiting for days straight, unable to breathe, feeling like I was going to die....

I have recently started reading up on cytokines, but I had not yet found anything like the article you posted. I think you're onto something, here.
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Re: Cytokine storm or immunopathology

Postby sizzled » Tue 30 Oct 2007 13:05

Is a herx a cytokine storm?

Is active infection (symptoms) a cytokine storm?

Is that why some doctors tell you to lower your dose of abx or take a few days off??? Is that a case for needing a dose or two of steroids??

Can cytokines be measured to determine what an allergic reaction is versus a herx?

Sorry if I am being dense here.
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Re: Cytokine storm or immunopathology

Postby cave76 » Tue 30 Oct 2007 17:09

sizzled wrote:

Is a herx a cytokine storm?

Is active infection (symptoms) a cytokine storm?

Is that why some doctors tell you to lower your dose of abx or take a few days off??? Is that a case for needing a dose or two of steroids??

Can cytokines be measured to determine what an allergic reaction is versus a herx?


You're NOT being dense! Or, if you are, so are a lot of researchers, llmds and myself included.

It's a gnarly topic. And hard to prove or disprove with certainty.

My 'guesses':

I think that's why we're sometimes told to back off for a while. Just in case.

[Remember, one person's 'unbearable' herx is another's minor downturn that doesn't keep them from shopping at the mall. LOL --- Yes I've seen that!!! <g> A doctor may have a hard time 'reading' that patient, unless he's known them for a while.]

An 'allergic' reaction 'usually' comes with swollen throat/difficulty breathing and swallowing, hives or severe rash all over.
But I'm sure there are all sorts of variations.

If you get the above----- get to the ER! ASAP

I don't know about measuring a herx. Maybe someone else does?
I'm also not sure if ongoing infection is a cytokine storm. I doubt it. Anyone?

NO steroids---- unless it's necessary, per your llmd.

There's more we don't know about these diseases than we do know. :(
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Re: Cytokine storm or immunopathology

Postby LymeEnigma » Tue 30 Oct 2007 17:23

I wonder if finding a way to control the cytokines without disrupting the immune system too much might be an option in the future, at least for some symptom management...?
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Re: Cytokine storm or immunopathology

Postby cave76 » Wed 31 Oct 2007 15:33

You may be right, LE, about the immune system.

But that brings up my favorite (NOT) conundrum or puzzle---- Our immune system.

All I know about the immune system, besides the fact that it has two parts (so far): innate and acquired, is
that they're incredibly complex! Tweak one part, the other reacts. And I don't think that even the best researchers know just how it works.

But that's another story.
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Re: Cytokine storm or immunopathology

Postby Nick » Thu 1 Nov 2007 23:18

LymeEnigma wrote:I wonder if finding a way to control the cytokines without disrupting the immune system too much might be an option in the future, at least for some symptom management...?

that sounds totally impossible to me at least for the near future, if only because we hardly know how the cytokine system works and it is a system with lots of feedback loops ...
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Re: Cytokine storm or immunopathology

Postby Nick » Thu 1 Nov 2007 23:33

cave76 wrote:I don't know about measuring a herx. Maybe someone else does?
I'm also not sure if ongoing infection is a cytokine storm. I doubt it. Anyone?

yes, so many questions, so little answers...

I think it should be possible to measure a REAL herx e.g. by checking for bacterial die-off products and some host reactions to that in the blood. But then, most of the 'herxes' in lyme (with or without AB treatment) are probably not real herxes by definition.

ongoing infection is certainly not a cytokine storm. I think measuring cytokines in vivo is not an option yet, maybe in ten years or so by using special (inserted) testing chips.

Shortly before my first AB Lyme treatment started I was very ill for a few days (feeling very feverish in the brain/spinal chord, headaches, cold/warm sensations, strong sweats, hallucinations and frightening/violent dreams to name a few symptoms). Shortly after that started I noticed a peculair Selenium-like smell in my urine that was like dead, anaerobic bacteria to me (I'm a biochemist so I have experience some with that). I had never smelled it before, it stopped a few days after the high fever/sweats. I smelled it again a few weeks later when my IV rocephin treatment had started (doc was convinced by then I had stage 3 neuroborreliosis). When asking my neurologist he told me that several other patients had also reported this very peculiar smell in their urine in the first days after starting AB treatment. I'm pretty sure it must be a Bb die-off product ... With my later oral AB treatments I have never smelled it again, despite very severe herx reactions (especially from the metronidazol). A clinic with a good number of lyme patients and a research lab should be able to detect the components involved.
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Re: Cytokine storm or immunopathology

Postby lou » Fri 2 Nov 2007 2:08

I was tested for several cytokines, so it is possible to do in vivo. However, if the production of these cytokines is cyclic and no one knows how much is too much, or not enough, these results will be hard to interpret.

And the distinction between immunopathology and cytokine storm (herx) may not be all that clear. Here is an article on the subject. There are a lot more I could post, but the bottom line is that they do not know enough yet about the immune system to regulate it. The attempts so far have suggested unwanted side effects may occur.

Antimicrob Chemother. 1998 Jan;41 Suppl A:25-9.
Cytokines involved in human septic shock--the model of the Jarisch-Herxheimer reaction.
Griffin GE.

Division of Infectious Diseases, St George's Hospital Medical School, Tooting, London, UK.

Studies of the cytokine cascade in animal models of infection and human experiments involving endotoxin infusion have contributed fundamentally to understanding the role of cytokines in human sepsis. The complexity of this cytokine cascade has been difficult to unravel in clinical sepsis. However, the Jarisch-Herxheimer reaction has been identified as a model of the cytokine cascade in human sepsis and has provided an excellent model for experiments involving blocking agents. TNF blocking has been shown to be important for protection in animal models of sepsis, but has been somewhat disappointing in humans because adverse events have generally outweighed benefits.

PMID: 9511083 [PubMed - indexed for MEDLINE]

Free full text of this available by going to pubmed
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Re: Cytokine storm or immunopathology

Postby Nick » Fri 2 Nov 2007 11:31

lou wrote:I was tested for several cytokines, so it is possible to do in vivo. However, if the production of these cytokines is cyclic and no one knows how much is too much, or not enough, these results will be hard to interpret.

yes, we need some kind of measuring device that can check levels of many important cytokines around the clock (e.g. every hour) and in several different people, to get an idea how much levels fluctuate. Drawing blood every hour is not an option (I guess they need more than just a small drop for these test) so the only option would be some kind of chip that is in the blood flow and that is sensitive for these substances. Such chips are made on an experimental basis now (e.g. a Dutch company makes a chip that can monitor blood levels of certain antibiotics) and maybe technology like that could be used in the future for cytokines too.
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