I have been researching this with some interest because it is now suspected that many young, otherwise healthy people died of this in the Flu Pandemic of 1918. It is well known that the some of the survivors awoke some sixty years later with Parkinsonism and this is how levodopa was "discovered". They have been trying to directly link the flu virus to Parkinson's but I am thinking that these folks who were strong enough to survive the storm ended up with a low level inflammatory reaction that resulted in symptoms of PD (cant say it is same as Idiopathic, but there are people with post-encephalalytic PD that pass for idiopathic kind). Who knows? What sucks is that no one ever seems to explore these things further! See #27 "I can't Talk" Nicotine has also restored speech in a PWP.

Further support:

Cytokines formed of macrophages are a key part of PD pathology.
www.cytokinestorm.com

Cytokine storms are also implicated in deaths due to H1N1 and SARS. There have been case studies of young survivors of these viruses coming out of coma with Parkinsonism. Most recent example in 2009 in a 22 yr. old girl.

Journal of Neuroinflammation: Hypothalamic Abnormalities and Parkinsonism.


The only substance that is known to stop a cytokine storm is nicotine. Is this, in turn why nicotine is considered neuroprotective against PD?
How Nicotine Stops Inflammation - Scientific American 2006

The existing research shows, in no particular order, all of the following:
1- A fetus exposed in the womb to bacterial toxins develops a hypersensitivity and an over-reaction to future exposure to that toxin. Since that toxin is everywhere (it makes up over half of the volume of common house dust for example) that exposure is inevitable.
2- Further exposure to the toxin results in reactions within both the central and peripheral nervous systems. The peripheral reaction (outside the BBB) has been observed to last a matter of hours. Within the BBB, however, the reaction has been observed going strong ten *months* later.
3- This reaction churns out cytokines - protective chemicals in an acute time frame but destructive in the chronic.
4- Cytokines are neuroactive and function as neurotransmitters. They change the way our brains work and how we think and how our bodies work.
5- Cytokines are perceived by the stress systems as a stressor and the endocrine system responds by releasing cortisol and other steroidal hormones - protective in acute situations and destructive in the chronic. See #3 above. They are also neuroactive and influence mental function. See #4.
6- Just as cytokines increase hormonal production, the increased hormonal levels increase cytokines in a feedback loop. Acute advantage but chronically destructive.
7- This all begins with the immune response and gradually draws in the endocrine. That beginning can be in the womb as described yielding young onset. It can begin with a virus as a young adult or it can begin with a natural part of aging yielding senior onset.
8- Once this reaction is established, a large number of stimuli can set it off. Mercury. Manganese. Agricultural dust. Gases released in the shower by ground water. Milk contaminated with the heat resistant toxins. Stress.
9- This ongoing inflammatory response can lead to increased permeability in the lining of the gut as well as in the much discussed BBB.
10- Secondary infections such as UTIs and bad teeth can kick it all into overdrive and rapid decline results.
11- Chronic stress serves as a constant goad to keep the process rolling.
12- Cytokines and stress hormones chronically encountered result in damaged neurons.

Simple.

Actor Peter Falk ("Colombo") died recently of Alzheimers. While two different diseases, AD and PD have a lot in common. In the following article from today's British paper "The Daily Mail" you can just about replace AD with PD verbatim. And tumor necrosis factor is the most destructive of the cytokines.

<begin quote>
Did a trip to the dentist accelerate Columbo's Alzheimer's?

Yet at the beginning of 2007 he was still intellectually sharp enough to be working. But within weeks he ‘rapidly slipped into dementia after a series of dental operations’,....

A further deterioration followed in 2010 when he underwent hip-replacement surgery.....

Now, new research published in the journal Neurology could help to solve the mystery of how the actor became so ill so suddenly.

Researchers from Southampton University report compelling evidence that surgery, as well as injury and infection, can dramatically accelerate the disease and the rate of brain death in people who already have early Alzheimer’s disease.

The first stages of this type of dementia make the brain abnormally sensitive to the inflammatory proteins that the body produces to promote recovery, triggering severe Alzheimer....

The most significant of these proteins is tumor necrosis factor, a naturally-occurring substance that plays an essential role in the body’s immune response and the ability to recover from what doctors call ‘assaults’ on the body (bacterial or viral infections, injuries, surgery or heart attacks). It works by inducing ‘sickness behaviour’ such as a lack of energy, low mood and inability to concentrate.

‘As scientists, we’ve paid too little attention to this important process by which the brain responds to an infection or injury, by releasing a cascade of these inflammatory proteins into other parts of the body,’

This is just one of dozens of papers and green tea is just one of many plant-based anti-inflammatory compounds-


1. J Nutr. 1998 Dec;128(12):2334-40.

Green tea polyphenols block endotoxin-induced tumor necrosis factor-production
and lethality in a murine model.

Yang F, de Villiers WJ, McClain CJ, Varilek GW.

Graduate Program in Nutritional Sciences, Department of Internal Medicine,
University of Kentucky, Lexington, KY 40536, USA.

Green tea polyphenols are potent antioxidants. They have both anti-cancer and
anti-inflammatory effects. However, their mechanisms of actions remain unclear.
In inflammation, tumor necrosis factor-alpha(TNFalpha) plays a pivotal role.
NF-KB, an oxidative stress -sensitive nuclear transcription factor, controls the
expression of many genes including the TNFalpha gene. We postulated that green
tea polyphenols regulate TNFalpha gene expression by modulating NF-KB activation
through their antioxidant properties. In the macrophage cell line, RAW264.7,
(-)epigallocatechin gallate (EGCG), the major green tea polyphenol, decreased
lipopolysaccharide (LPS)-induced TNFalpha production in a dose-dependent fashion
(50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNFalpha mRNA
expression and nuclear NF-KB-binding activity in RAW264.7 cells (30-40%
inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNFalpha
production in elicited mouse peritoneal macrophages. In male BALB/c mice, green
tea polyphenols (given by oral gavage 2 h prior to an i.p. injection of 40 mg
LPS/kg body wt) decreased LPS-induced TNFalpha production in serum in a
dose-responsive fashion. At a dose of 0.5 g green tea polyphenols/kg body wt,
serum TNFalpha was reduced by 80% of control. Moreover, 0.5 g green tea
polyphenols/kg body wt completely inhibited LPS-induced lethality in male BALB/c
mice. We conclude that the anti-inflammatory mechanism of green tea polyphenols
is mediated at least in part through down-regulation of TNFalpha gene expression
by blocking NF-KB activation. These findings suggest that green tea polyphenols
may be effective therapy for a variety of inflammatory processes.


PMID: 9868178 [PubMed - indexed for MEDLINE]

Wow!

I am bummed to hear how he declined so rapidly and really is even more sad if what we're saying is true. They have been able to nip this if treated properly straight away. I always loved his acting. Read he was a cult phenomenon in Germany; too bad things didn't start there...he may still be here.

The relationship between stress and cytokines could be why we experience an exacerbation of symptoms under stress; illness can cause stress too.

I have read recently that we indeed have 70% of our entire brain's innate neurons intact. The Ventral Tegmental Area in midbrain that controls our limbic system and reward center has original store of dopa neurons. How can this be?
Turns out they are resistant to alpha-synuclein, but how do they escape the onslaught of cytokine production or are not targeted in immune system pathology like in the substantia nigra?

If we can connect these dots, you know that at least one researcher has done the same thing, so has someone tested the cytokine storm connection and we don't know that?

Also interesting you mention a "sickness behaviour" emerged in P. Falk. It sounds eerily similar to Encephalitis Lethargica which is what emerged after 1918 flu and preceded the Parkinsonism. Could this also reflect our sleep anamolies?

Laura

I don't know why Laura, but I have a feeling that it is specifically through the neuromelanin , it seems to me the only thing different. It's not scientific, it's a hunch. Why else would other neurons doing the same job survive.........