Exercise, Reactive Oxygen Species, and Fatigue.

Croatoan

Well-Known Member
It's essentially the hit and run theory (his) vs. the persistent infection theory (mine). Still a very active area of ME research.

He is saying that an initial trigger causes run away ROS production due to the inability to neutralize it. I'm saying that there is an ongoing stressor that is perpetually causing the ROS production as part of the immune response. Both theories seem to fit the observed clinical picture, we may someday learn that both are happening in various subsets of patients.

I was getting stuck on his insistence that vitamin deficiency alone causes ROS production, but after rereading most of the thread I don't think that he was intending to argue that, even though that's what he said at several points. I think he is asserting that it is always in combination with some stressor to trigger the ROS production in the first place.

I agree that this is part of it but it's not the whole story. It's this, as well as production of various cytokines, eicosanoids such as prostaglandins, purines, etc. All of the various danger signals that are part of the immune response that tell the body and brain that something is wrong and induce the symptoms we experience. The question that science has to answer still is if this is happening appropriately or inappropriately.
I think CFS can be caused without an initial viral infection as well, just to be clear. I think CFS can be caused by several things and one of them is a cofactor deficiency caused by genetic variants.

Anti-viral drugs, in my opinion, will only help CFS by assist the failing immune system. But the underlying issue will still be unresolved; high ROS caused by abnormal metabolism.
 

RuthAnn

Well-Known Member
I agree that this is part of it but it's not the whole story. It's this, as well as production of various cytokines, eicosanoids such as prostaglandins, purines, etc. All of the various danger signals that are part of the immune response that tell the body and brain that something is wrong and induce the symptoms we experience. The question that science has to answer still is if this is happening appropriately or inappropriately.
Good conversation, I am learning a lot.
So in your view, killing the pathogen would bring relief, since that is the cause of the ROS production?
And then with respect to cytokines, I just found this.

Pro-inflammatory Cytokines Increase Reactive Oxygen Species through Mitochondria and NADPH Oxidase in Cultured RPE Cells
 

Croatoan

Well-Known Member
Good conversation, I am learning a lot.
So in your view, killing the pathogen would bring relief, since that is the cause of the ROS production?
And then with respect to cytokines, I just found this.

Pro-inflammatory Cytokines Increase Reactive Oxygen Species through Mitochondria and NADPH Oxidase in Cultured RPE Cells
But this goes both ways. ROS can cause cytokine release.
http://www.ncbi.nlm.nih.gov/pubmed/20962773
http://www.ncbi.nlm.nih.gov/pubmed/23323860
http://www.ncbi.nlm.nih.gov/pubmed/16091123

same is true for the eicsanoids
http://www.ncbi.nlm.nih.gov/pubmed/1631318

So what we are seeing here is the difference between Immune vs auto-immune
 

weyland

Well-Known Member
I think I'm confused now. So here you say that people with ME cannot fight infection because of ROS (did you really mean exogenous ROS, i.e. ROS from outside the body?):
I think that rests my case that ME is not caused by an infection, but rather caused by the bodies inability to fight infection because of exogenous ROS production and a genetic susceptibility to certain vitamin deficiencies.
But now you are saying that more ROS = a stronger immune response (i.e. more production of cytokines, eicosandoids, etc.)

And this paper you linked shows that antioxidant therapy actually causes immunosuppression similar to what we were talking about before in T cells:
ROS modulation of T cell responses using SOD mimetics

As ROS are essential for initiating proinflammatory cytokine production and adaptive immune maturation, the generation of these highly reactive molecules should be regarded as a necessary proinflammatory-derived third signal for mediating effective adaptive immune activation. Redox modulation profoundly affects T cell responses, which has been illustrated with metalloporphyrin-based superoxide dismutase (SOD) mimetics that scavenge a wide array of ROS. Analysis of CD8+ T cell responses following treatment of lymphocyte choriomeningitis virus (LCMV)-infected mice with a SOD mimetic revealed significant reductions in circulating antigen–specific CD8+ T cells compared with vehicle treatment, indicating that ROS are critical for CD8+ T cell proliferation and antigen-specific clonal expansion.154 Further validating the crucial role of ROS in CD8+ T cell activity, Sklavos et al. demonstrated that ablation of free radicals via a SOD mimetic inhibited CD8+ T cell proliferation, proinflammatory cytokine production, and CTL target lysis, concomitant with profound reductions in perforin and granzyme B.73 In addition to affecting CD8+ T cells, a SOD mimetic induced CD4+ T cell antigen–specific hyporesponsiveness and reduced effector responses within polyclonal (BALB/c), autoimmune-prone (NOD), TCR transgenic (DO11.10, OT-II), and diabetogenic TCR transgenic (NOD.BDC-2.5) mouse strains.74 Importantly, SOD mimetic treatment of immunodeficient mice adoptively transferred with the BDC-2.5 CD4+ T cell clone provided significant protection against T1D by blunting IFN-γ production and T cell proliferation, illustrating the ability of ROS to modulate adaptive immune responses by influencing proinflammatory cytokine production.93 Thus, ablation of ROS reveals the potent effects of these highly reactive molecules on efficient adaptive immune maturation.
So increasing antioxidants might make it harder for the body to fight infection because of the key role ROS play in facilitating the immune cascade.
 

RuthAnn

Well-Known Member
But this goes both ways. ROS can cause cytokine release.
http://www.ncbi.nlm.nih.gov/pubmed/20962773
http://www.ncbi.nlm.nih.gov/pubmed/23323860
http://www.ncbi.nlm.nih.gov/pubmed/16091123

same is true for the eicsanoids
http://www.ncbi.nlm.nih.gov/pubmed/1631318

So what we are seeing here is the difference between Immune vs auto-immune
I don't fully understand it all, but I had been wondering why things like reishi and colostrum are immune system modulators and at the same time antiviral and antibacterial. The supplement that worked the best for my severe lung "infection" was apolactoferrin, and it remains the best remedy to this day when coughing starts. I first tried it as a remedy when I thought that I might have iron overload furnishing fuel to whatever pathogen was causing my symptoms. So although there appears to be no viral or bacterial "killer" in apolactoferrin, it relieves my lung symptoms. It worked, but my thinking may have been either wrong or incomplete.
I don't know if my symptoms are from autoimmune or immune, but now I am thinking more autoimmune.
 
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RuthAnn

Well-Known Member
Do you mean something like this?

"It is also well know that after stressful life events, high protein diet, high calorie diet, heat stress, exogenous toxins, and viral or bacterial infection and the inability to remove ROS.
These being the things that cause the ROS and one should work on to remove.

I believe that the ROS in genetically susceptible people (nature) becomes to much to handle after any combination of these environmental issues (nurture).
And then while you're doing that in order to remove symptoms try to help your body reduce the symptoms through various channels.

Your whole life should be focused on limiting the creation of, and reducing ROS if you want to feel better.
And if the symptoms don't stay away keep working at it so that you are as symptom free as you can be.

Something like that?
By the way, I cannot take credit for the words in black, they are from the original post, I was just expanding on them.
 

Croatoan

Well-Known Member
I think I'm confused now. So here you say that people with ME cannot fight infection because of ROS (did you really mean exogenous ROS, i.e. ROS from outside the body?):
sorry, I meant outside the body and outside the immune system as well. ROS is produced during normal meabolism.

But now you are saying that more ROS = a stronger immune response (i.e. more production of cytokines, eicosandoids, etc.)
No, I am saying it is an autoimmune disorder. Autoimmune disorders make us feel like we are sick when there is no pathogen.

And this paper you linked shows that antioxidant therapy actually causes immunosuppression similar to what we were talking about before in T cells:
So increasing antioxidants might make it harder for the body to fight infection because of the key role ROS play in facilitating the immune cascade.
Yes, immunosuppresion is needed in people who have autoimmune disorders.
 

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