Trial Report Heat treatment in health and disease: How water-filtered infrared-A (wIRA irradiation affects key cellular mechanisms in ME/CFS, 2024, Hochecker

[Dolphin]

https://www.sciencedirect.com/science/article/abs/pii/S0306456524000317

Journal of Thermal Biology
Available online 21 February 2024, 103813
In Press, Journal Pre-proof


Heat treatment in health and disease: How water-filtered infrared-A (wIRA irradiation affects key cellular mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS patients compared to healthy donors

Hochecker Barbara, Molinski Noah, Matt Katja, Meßmer Alica, Scherer Melanie, von Ardenne Alexander, Bergemann Jörg
a
Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Sigmaringen, Germany
b
Von Ardenne Institute of Applied Medical Research GmbH, Dresden, Germany
Received 25 April 2023, Revised 22 December 2023, Accepted 14 February 2024, Available online 21 February 2024.


https://doi.org/10.1016/j.jtherbio.2024.103813Get rights and content

Highlights

• •
  Autophagy is induced by wIRA treatment in healthy human fibroblasts.
  
  
• •
  Heat treatment leads to higher autophagy in healthy donors and ME/CFS patients.
  
  
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  Hyperthermia compensates for higher mitochondrial function in ME/CFS patients to the healthy level.
  
  
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  mRNA levels of MAP1LC3, SIRT1 and HSPA5 were significantly enhanced by wIRA irradiation.

Abstract

Heat treatment or hyperthermia is a promising therapy for many diseases, especially cancer, and can be traced back thousands of years.

Despite its long history, little is known about the cellular and molecular effects of heat on human cells.

Therefore, we investigated the impact of water-filtered infrared-A (wIRA) irradiation (39 °C, 60 min) on key cellular mechanisms, namely autophagy, mitochondrial function and mRNA expression, in human fibroblasts and peripheral blood mononuclear cells (PBMCs) from healthy donors and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients.

Our results show an induction of autophagy in healthy fibroblasts and PBMCs from healthy donors and ME/CFS patients.

ME/CFS patients have higher mitochondrial function compared to healthy donors.

The wIRA treatment leads to a slight reduction in mitochondrial function in PBMCs from ME/CFS patients, thereby approaching the level of mitochondrial function of healthy donors.

Furthermore, an activation of the mRNA expression of the autophagy-related genes MAP1LC3B and SIRT1 as well as for HSPA1, which codes for a heat shock protein, can be observed.

These results confirm an impact of heat treatment in human cells on key cellular mechanisms, namely autophagy and mitochondrial function, in health and disease, and provide hope for a potential treatment option for ME/CFS patients.

https://twitter.com/user/status/1761203992237924566

 

[NelliePledge]

We should put these guys in a room with the Polish team that use cold therapy.

 

[SNT Gatchaman]

Just skimming before dinner.

Their evaluation of fibroblasts and PBMCs at rest (before irradiation) replicates some of the initial findings in An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients (2020, International Journal of Molecular Sciences)

They show increased max OCR and spare reserve capacity in mitochondria.

Also finds increased autophagy, and the refer to Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products RAGE (2022, Molecular and Cellular Neuroscience)

 

[SNT Gatchaman]

I've read this paper through now and it's quite interesting. While they don't reference it, their baseline findings replicate the findings linked above. @DMissa if you haven't already seen it, this may be of interest. Highlighting from their discussion —

Surprisingly, autophagy and mitochondrial function data are higher in ME/CFS patients than in healthy donors. As the name suggests and mentioned in the introduction, fatigue is a major symptom in ME/CFS. Based on this fact, we suspected a lower activity of autophagy and mitochondrial function.

The obvious hypothesis of impaired mitochondrial function in ME/CFS initially seemed to be confirmed. For example, the work of Tomas et al. found a decrease in basal respiration, proton leak, maximal respiration and reserve capacity in PBMCs from ME/CFS patients (Tomas et al. 2017). These results are in contrast to our work, which showed an increase in these parameters. Interestingly, a study by the same research group two years later found that there were no differences in individual mitochondrial complex activity or respiratory activity between healthy controls and CFS in PBMCs (Tomas et al. 2019a). Another study showed that myoblasts grown in the presence of serum from patients with severe ME/CFS had increased mitochondrial respiration (Fluge et al. 2016), supporting our findings.

With our measurement method for examining mitochondrial function, we determine the oxygen consumption rate and not the actual ATP level. Therefore, we suspected that there might be mitochondrial dysfunction leading to inefficient ATP production with increased oxygen consumption.

These results could support our hypothesis that more oxygen is consumed but not more ATP is produced. Furthermore, there might be a dysfunction in non-mitochondrial ATP production.

Which I think corresponds to the more detailed findings in An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients (2020, International Journal of Molecular Sciences), which said —

As a proportion of the basal oxygen consumption rate (OCR), the rate of ATP synthesis by Complex V was significantly reduced in ME/CFS

The foregoing data shows that mitochondrial respiratory capacity in ME/CFS lymphoblasts is upregulated, perhaps in response to inefficient ATP synthesis by Complex V. This is coupled with increased depletion of energy by transport processes which we hypothesized would include those that provide oxidizable substrates to the mitochondria. We therefore expect the rates of nonmitochondrial catabolic processes that provide these substrates also to be increased. Our data supports such a possible shift in metabolism as the “nonmitochondrial” OCR, an indicator of catabolic rate, was significantly elevated in ME/CFS lymphoblasts.

 

[SNT Gatchaman]

In methods they say —

Human PBMCs were isolated from 36 mL of human blood using Leucosep tubes ([...]) according to the manufacturer's instructions. PBMCs were resuspended in phosphate-buffered saline (PBS) and cell counts were determined using a Luna-FL™ automated cell counter ([...]). Treatment with wIRA hyperthermia and subsequent measurements of mitochondrial respiration were performed with freshly isolated PBMCs. For autophagy assay and mRNA expression analysis, the remaining cells were seeded in RPMI1640 medium without phenol red containing 20% FBS and incubated overnight at 37°C and 5% CO2.

Human PBMCs were seeded in RPMI1640 medium without phenol red and treated in the IRAcubator ([...]) with wIRA irradiation for 60 min at 39 °C or for 60 min at 37 °C with 5% CO2 as control. Cells were treated separately for each assay to ensure that all measurements were performed immediately after treatment.

So the mitochondrial studies were after 60 minutes for heated and controls, not overnight which might see them dying off as discussed in Missailidis et al.

Interestingly, treatment with wIRA irradiation leads to a compensation of the oxygen consumption rate in all measured mitochondrial parameters of ME/CFS patients and decreases them to the same level as in healthy donors. This effect is only present in ME/CFS patients.

I doubt this could be relevant to any meaningful practical therapies, but if this finding were unique to ME/CFS (and not seen in eg MS), then maybe it could form a clinical test??

 

[Joan Crawford]

Interesting to see this study.

I've used the Iratherm bed at the Breakspear. After my first session I felt like the relaxed, pleasant feeling that i used to get pre illness after completing some hard physical exercise. It was a really good feeling.

I suspect this may well help pwME; however, patients need to be well enough to be able to do this therapy. I suspect it's not for the severely affected. It might be more doable for patients when we have other treatments and this might be supportive. Helped to get me back into exercising.