I'm trying to understand. So a couple of these cytokines are high enough to reflect that some physiological problem is definitely going on somewhere in the body and these cytokine results in short duration do reflect this quite clearly? So even though the cytokines themselves are not at levels to cause symptoms ( I read that they don't correlate with symptoms) these findings are adequately reflective of something going on biologically elsewhere to make this very significant? Any chance you could give a 101 how we know these could reflect that something else is happening. I'm trying to understand how the difference between short duration and healthy controls is enough to show this to doctors and researchers.
I had thought that the increase compared to controls in short duration and then the drop in long duration was also significant. Do you think this paper will be taken notice of really seriously in the medical community?
Take as an example the biochemical changes in the blood in RA. It is very hard to measure TNF but it is now reasonably reliable and we have several bits of evidence indicating that TNF actually causes pain and exhaustion, as well as bone damage. In the old days we measured ESR, which is mostly a reflection of fibrinogen levels which go up because IL-6 has gone up. And IL-6 goes up partly because TNF goes up and it also contributes to B cell activation and disease. But fibrinogen probably does not do anything much.
Basically, immunological diseases set off very complex networks of signals and in each disease it is a different subset of these signals that actually causes trouble. And what you can measure may not be the signals that cause the trouble. What this study is saying is that if you listen at the door of the immune system you can definitely hear some plotting of crime inside, but you don;t know which of the people speaking is going to go out and commit it. And after 3 years they are still committing the crime (because the PWME is still ill) but they are no longer even talking about it - something like that.
So there is no suggestion from Dr Hornig and Dr Lipkin that they have found the mechanism here - just some incriminating evidence. But that is where we need to start. I asked Dr Lipkin about blocking IL-17 in Bristol, rather jokingly, and he said no way would he say he had enough evidence to do that. (He may be more sensible than me.)