Interleukin-1-related activity and hypocretin-1 in cerebrospinal fluid contribute to fatigue in primary Sjögren’s syndrome, 2019, Omdal et al

[Andy]

Background
Fatigue is a common and sometimes debilitating phenomenon in primary Sjögren’s syndrome (pSS) and other chronic inflammatory diseases. We aimed to investigate how IL-1 β-related molecules and the neuropeptide hypocretin-1 (Hcrt1), a regulator of wakefulness, influence fatigue.

Methods
Hcrt1 was measured by radioimmunoassay (RIA) in cerebrospinal fluid (CSF) from 49 patients with pSS. Interleukin-1 receptor antagonist (IL-1Ra), IL-1 receptor type 2 (IL-1RII), IL-6, and S100B protein were measured by enzyme-linked immunosorbent assay (ELISA). Fatigue was rated by the fatigue visual analog scale (fVAS).

Results
Simple univariate regression and multiple regression analyses with fatigue as a dependent variable revealed that depression, pain, and the biochemical variable IL-1Ra had a significant association with fatigue. In PCA, two significant components were revealed. The first component (PC1) was dominated by variables related to IL-1β activity (IL-1Ra, IL-1RII, and S100B). PC2 showed a negative association between IL-6 and Hcrt1. fVAS was then introduced as an additional variable. This new model demonstrated that fatigue had a higher association with the IL-1β-related PC1 than to PC2. Additionally, a third component (PC3) became significant between low Hcrt1 concentrations and fVAS scores.

Conclusions
The main findings of this study indicate a functional network in which several IL-1β-related molecules in CSF influence fatigue in addition to the classical clinical factors of depression and pain. The neuropeptide Hcrt1 seems to participate in fatigue generation, but likely not through the IL-1 pathway.

Open access at https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1502-8

 

[Alvin]

I have dug deeply into this on the past and its highly unlikely Hypocretin-1 (also known as Orexin-1) has anything to do with ME

 

[Kalliope]

I listened to a lecture by Omdal yesterday. He's taken a PhD on cognitive dysfunctions in autoimmune diseases and realised how big fatigue is as a problem. He said that earlier fatigue was regarded as something functional, psychiatry, but he later got convinced that there must be a biology behind fatigue.

He talked about fatigue appearing in depression, sleep disorders, cancer, neurodegenerative conditions, infections, chronic autoimmune inflammatory diseases, stroke etc. Put together this represents a big group of people suffering from fatigue.

ME on the other hand he said constitutes a very small percent of the population but dominates in the media when the subject is fatigue. The main problem according to him lies in the big group suffering from fatigue, those with an underlying chronic condition. In his world ME is a condition dominated by fatigue but without any underlying illness.

 

[Midnattsol]

I listened to a lecture by Omdal yesterday. He's taken a PhD on cognitive dysfunctions in autoimmune diseases and realised how big fatigue is as a problem. He said that earlier fatigue was regarded as something functional, psychiatry, but he later got convinced that there must be a biology behind fatigue.

He talked about fatigue appearing in depression, sleep disorders, cancer, neurodegenerative conditions, infections, chronic autoimmune inflammatory diseases, stroke etc. Put together this represents a big group of people suffering from fatigue.

ME on the other hand he said constitutes a very small percent of the population but dominates in the media when the subject is fatigue. The main problem according to him lies in the big group suffering from fatigue, those with an underlying chronic condition. In his world ME is a condition dominated by fatigue but without any underlying illness.

Good thinking om fatigue as a problem for many people, weird conclusion about ME.

 

[rvallee]

I listened to a lecture by Omdal yesterday. He's taken a PhD on cognitive dysfunctions in autoimmune diseases and realised how big fatigue is as a problem. He said that earlier fatigue was regarded as something functional, psychiatry, but he later got convinced that there must be a biology behind fatigue.

He talked about fatigue appearing in depression, sleep disorders, cancer, neurodegenerative conditions, infections, chronic autoimmune inflammatory diseases, stroke etc. Put together this represents a big group of people suffering from fatigue.

ME on the other hand he said constitutes a very small percent of the population but dominates in the media when the subject is fatigue. The main problem according to him lies in the big group suffering from fatigue, those with an underlying chronic condition. In his world ME is a condition dominated by fatigue but without any underlying illness.

Pretty good example of what the problem is, how flawed the thinking about fatigue is in medicine, what it even means at all and how confusion arises from people who look at patients with a high number of symptoms and decide to call it fatigue despite the patients saying "wait, no, you dismissed most of what I said, why would you do that?".

It's almost impossible to progress when researchers arbitrarily redefine the meaning of common words or choose to lump a number of symptoms, mash them together in a rough square shape and fail at making it fit in a round hole while saying it's good enough. Even from people who seem to start getting that entirely ignoring one of the most common symptoms in medicine isn't the smart thing some think it is.

I don't know what it will take to get through that rapid fatigability is its own separate thing and that ignoring symptoms for arbitrary reasons helps no one make any progress. Well, obviously that would be the whole "patient engagement" thingy I hear so much about and can't wait to actually begin.

 

[Mithriel]

It sounds like he believes ME is just fatigue. That is what happens when all the other symptoms of ME are ignored by the "experts" and their research. It is like saying MS is just fatigue by ignoring the paralysis.

 

[Snow Leopard]

I listened to a lecture by Omdal yesterday. He's taken a PhD on cognitive dysfunctions in autoimmune diseases and realised how big fatigue is as a problem. He said that earlier fatigue was regarded as something functional, psychiatry, but he later got convinced that there must be a biology behind fatigue.

He talked about fatigue appearing in depression, sleep disorders, cancer, neurodegenerative conditions, infections, chronic autoimmune inflammatory diseases, stroke etc. Put together this represents a big group of people suffering from fatigue.

ME on the other hand he said constitutes a very small percent of the population but dominates in the media when the subject is fatigue. The main problem according to him lies in the big group suffering from fatigue, those with an underlying chronic condition. In his world ME is a condition dominated by fatigue but without any underlying illness.

Sigh. The difference is that ME patients are often much more severely impacted.

Fatigue itself has many potential causes, because it is a proprioceptive phenomenon. Fatigue is not pain. Fatigue due to nerve blockage is different from fatigue due to sclerotic lesions, which is different to lesions or injury of the brain stem, which is different from mitochondrial myopathies, which are different from dystrophies, which are different from other metabolic disorders and severe nutrient deficiencies.

Omdal doesn't seem to understand that fatigue is not simply signalled through chemoreceptors, something he should have realised by the fact that IL-1 or HSP90 or whatever he has latched onto these days is not consistently associated with fatigue across the diverse group of patients that he cited. Admittedly, many researchers of ME and CFS have made the same mistake.
Aside, he also uses lower quality methodology - visual analogue scales are a relative scale, and so if you wish to associate quantity of a particular biomarker with the outcome, the study must be self controlled, namely increases in the VAS for a given participant should be associated with an increase in the biomarker in question.

 

[Mithriel]

And the underlying irony of it all is that fatigue was not a required symptom for ME. I never experienced fatigue and only have a little now after 50 years. I feel fine until I suddenly stop - fatiguability. One day I began to experience fatigue but it turned out to be diabetes. It was different from what usually happens. Other things like pain cut in before I get fatigue.