ME/CFS, also known as chronic fatigue syndrome, is a serious, systemic, chronic illness that significantly impairs the quality of life of those affected. The disease often debuts at the same time as an infection.
Study
The study, which included 31 patients, was a double-blind, randomized, placebo-controlled study conducted in 2018–2019 at the Neurological Rehabilitation Clinic at Stora Sköndal, Stockholm. It was initiated by senior physician Dr. Per Julin and Petter Brodin, who is a pediatrician and professor of pediatric immunology. INMEST was administered by staff at the clinic.
Patients received either active INMEST or placebo twice a week for the first four weeks, after which all patients received active INMEST twice a week for the subsequent four weeks.
Results
No treatment effect was seen on fatigue. However, both the group that initially received placebo and the group that always received active INMEST reported reduced disease symptoms, as measured by a questionnaire. In the questionnaire, patients rated 14 common ME symptoms on a 5-point scale (none, mild, moderate, severe and unbearable): tender lymph nodes; palpitations; fever; orthostatic dizziness; irritable bowel syndrome; sleep disturbances; numbness and paresthesia; joint pain; general pain; body aches; difficulty concentrating; memory problems; chills and sweating and headache.
The improvement measured by this scale was approximately twice as great in the group receiving active INMEST compared to those receiving placebo, during the first half of the study. During the remainder of the study when all patients received active INMEST, both groups continued to improve, and again the improvement was more pronounced in the group that received active INMEST throughout. The symptom relief in the group that received active INMEST at all times was from the beginning to the end of the study (after 16 treatments with INMEST) ~30% and this was a statistically significantly more pronounced symptom reduction compared to the group that received placebo during the first half of the study (p=0.00003). The symptom relief seen in both groups after the treatment period was maintained over the following three months.
To study how repeated INMEST treatment affects the body, blood samples were taken before the start of the study, after four weeks of treatment, and after eight weeks of treatment with INMEST. A series of advanced analyses were performed on the blood samples. Among other things, the composition of immune cells and their surface structures were studied using mass cytometry. In addition, proteins in the blood were examined with the help of Olink analyses using three so-called panels measuring proteins of importance in inflammation and for cell metabolism and functioning of the nervous system. So-called mRNA sequencing was also done to determine to what extent different genes were expressed.
The study showed that the most upregulated gene with INMEST was UBE2H, which stimulates ubiquitin-mediated degradation of dysfunctional proteins. In addition, INMEST increased the gene expression of SIRT1, a response pathway that counteracts oxidative stress. There was also an improvement in energy metabolism in so-called mononuclear cells (which include several types of cells in the immune system). In addition, IL-17A was one of the proteins that decreased the most after INMEST treatment, and IL-17A is believed to contribute to chronic inflammation.
Finally, with INMEST, an increased proportion of specific regulatory T cells and a decreased proportion of effector cells were observed. T cells are important for maintaining balance in the gut, and effector cells are known to interact with microbes in the gut and promote inflammation.
This study is published in 2023 in Oxford Open Immunology and can be read in full for free at: