The Problem(s) with "Inflammation"

[Jonathan Edwards]

You could have 10 different pathogenic/inflammatory triggers causing the same downstream causal pathway patholgy in people prone for ME/CFS, but finding 'the missing link' via just one of these triggers (and if it's by accident) might illuminate the whole thing?

Of course. Nobody is disputing that.

To think of perhaps EBV and its potential implications for MS as a permissive step would be more useful in terms of ME/CFS?

It still isn't part of the concept of MS. One day someone may provide a case report of MS in someone who has never encountered EBV. Otherwise, the concept of MS might shift to include the presumption of EBV infection being a step in the common process but it has not so far. Similarly, for ME/CFS the concept does not include any specific inflammatory step as of now.

How can there be any evidence for the relevance of the acute stage if we only study patients at the six-month cutoff, Dr. Edwards?

That isn't what my comment was referring to but I agree that only studying people after 6 months is a problem. But I don't think it is particularly relevant to this discussion. The references to inflammation that I have complained about are universally about inflammation being the result of ME/CFS processes - they all say "and that leads to inflammation". And yet there isn't any at that point (which as you say will be 6 months down the line).

 

[butter.]

Of course. Nobody is disputing that.


It still isn't part of the concept of MS. One day someone may provide a case report of MS in someone who has never encountered EBV. Otherwise, the concept of MS might shift to include the presumption of EBV infection being a step in the common process but it has not so far. Similarly, for ME/CFS the concept does not include any specific inflammatory step as of now.


That isn't what my comment was referring to but I agree that only studying people after 6 months is a problem. But I don't think it is particularly relevant to this discussion. The references to inflammation that I have complained about are universally about inflammation being the result of ME/CFS processes - they all say "and that leads to inflammation". And yet there isn't any at that point (which as you say will be 6 months down the line).

I definitely agree with you that there is no evidence—apart from a slight increase in CRP in the DecodeME dataset—for ‘classical inflammation’ in ME/CFS as it is currently defined.

I think there might be evidence for micoglial activation (to use your preferred term) with as of yet unclear consequences.

 

[Annavive]

I was hospitalised for a serious infection and CRP was fine and was for those initial years.

I walked around with a very severe bacterial infection for years, I was also hospitalised and my CRP was close to 0.
I was diagnosed with ME/CFS after all types of blood tests, MRI etc was conducted, consistenly low CRP - which was tested regularly (once every two weeks). It took a year and multiple doctor visits monthly and referrals to get my diagnosis. A ME/CFS clinic diagnosed me upon fitting the CCC. After my diagnosis I still kept pushing for infectious testings as I had done the whole year.

After 2 years, a bacteria that haden´t been tested for before was found. Doctors refused to treat it with antibiotics since CRP was absent. According to my country medical system, absence of CRP means that an infection should not be treated, rather monitored if it gets worse. I kept testing positive for the infection for the next couple of months, and my CRP kept being close to 0. Eventually my doctor decided to treat the infection with two weeks of strong antibiotics. Right after the course, all my symptoms had vanished, except some mild fatigue and brainfog. Each week my fatigue kept improving until I no longer suffered from symptoms. I was able to fully return to school and participate in every gym class and exercise.

After 5-6 years of being in remission I caught another unknown infection. A year of asking for infectious testings and more, I was again rediagnosed with ME/CFS. My CRP once again is close to 0. All other inflammation markers tested are low, neutrophils, WBC and more. However, during the course of my second time with ME/CFS I had different bacterial infections such as strep throat, pelvic inflammatory disease (caused by bacteria), a staph skin bacterial infection and more, my CRP has always been under 5. I have experienced permanent improvement of my baseline following specific antibiotics during this time, and no improvement at all following other antibiotics.

No, there are a variety of organisms that can infect us with essentially no inflammatory response - nematodes for instance. The HIV virus does not cause inflammation until secondary events occur. There are human retroviruses that get incorporated without any obvious pathology as far as I am aware.

But it isn't that relevant. ME/CFS is what we call the process that is often a sequel to an infection. The infective event isn't ME/CFS. Any more than strep throat is rheumatic fever.

It is dangerous and irresponsible to assume that an ongoing infection has no relevance to ME/CFS. There is a growing body of research showcasing how persistent infections (fungi, bacterial, viral and parasitic) and/or persistent viral load can lead to the pathology in ME/CFS and drive symptoms. There is a few autopsy studies also contributing to that evidence. We cannot be certain that pathogens drives the disease, however, saying it isn´t relevant and that ME is sequel to an infection is not something we can be sure of either.

 

[Jonathan Edwards]

There is a growing body of research showcasing how persistent infections (fungi, bacterial, viral and parasitic) and/or persistent viral load can lead to the pathology in ME/CFS and drive symptoms.

'A growing body of research' nearly always means that there is a fashion for hoping that something reliable has been found but it hasn't yet. We cannot exclude anything but the reliable evidence at present is zero. Anyway, that post was making a different point - that 'ME/CFS' is not equated with the trigger infective event when it follows an infection that resolves a point about terminology, not biology.

 

[poetinsf]

Late to the party as usual. My pet peeve is the Columbia U study in 2015 that found hyperactive immune system in the first 3 years and then the depressed one after that, thus concluding that inflammation level does not predict the symptom severity. Then another paper in 2025 by the same core team declared there is a chronic inflammation in ME/CFS, without any reference to their first paper. Both used cytokine levels as the marker of inflammation, I believe. (The second paper also refers to interferon level). All I could conclude from this was that inflammation in ME/CFS is a red herring like many abnormalities in ME/CFS.