Major Study Finds Immune Downregulation Over Time in Chronic Fatigue Syndrome


Founder of Health Rising and Phoenix Rising
Staff member
Similar to what the Lipkin/Hornig study found, this large study - 100 patients - found significant reductions in some cytokines in longer duration patients vs health controls. This suggests that immune systems becomes downregulated not upregulated over time. That of course suggests that immune boosters might be helpful.

This study looked at some different immune factors than did the Lipkin Hornig CFI study. Two of immune factors that were downregulated were not measured in the CFI stuidy.

Many of the factors that were downregulated in the CFI study were not significantly downregulated in this study. The broad trend of reduced immune activation was the same, but for the most part different immune factors unfortunately showed up in both studies. This is pretty much par for the course for cytokine studies...

Some immune factors were upregulated; one of which - eotaxin - was upregulated in the Lipkin Hornig study. That was good news.

I'm not at all clear how this immune downregulation fits - if it fits at all with the Rituximab results. Rituximab is reducing the activation of some parts of the immune system.

Cytokine. 2015 Nov 23;78:27-36. doi: 10.1016/j.cyto.2015.11.018. [Epub ahead of print] Reductions in circulating levels of IL-16, IL-7 and VEGF-A in myalgic encephalomyelitis/chronic fatigue syndrome.
Landi A1, Broadhurst D2, Vernon SD3, Tyrrell DL4, Houghton M5.
Author information

Recently, differences in the levels of various chemokines and cytokines were reported in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as compared with controls. Moreover, the analyte profile differed between chronic ME/CFS patients of long duration versus patients with disease of less than 3years.

In the current study, we measured the plasma levels of 34 cytokines, chemokines and growth factors in 100 chronic ME/CFS patients of long duration and in 79 gender and age-matched controls. We observed highly significant reductions in the concentration of circulating interleukin (IL)-16, IL-7, and Vascular Endothelial Growth Factor A (VEGF-A) in ME/CFS patients. All three biomarkers were significantly correlated in a multivariate cluster analysis.

In addition, we identified significant reductions in the concentrations of fractalkine (CX3CL1) and monokine-induced-by-IFN-γ (MIG; CXCL9) along with increases in the concentrations of eotaxin 2 (CCL24) in ME/CFS patients.

Our data recapitulates previous data from another USA ME/CFS cohort in which circulating levels of IL-7 were reduced. Also, a reduced level of VEGF-A was reported previously in sera of patients with Gulf War Illness as well as in cerebral spinal fluid samples from a different cohort of USA ME/CFS patients. To our knowledge, we are the first to test for levels of IL-16 in ME/CFS patients.

In combination with previous data, our work suggests that the clustered reduction of IL-7, IL-16 and VEGF-A may have physiological relevance to ME/CFS disease. This profile is ME/CFS-specific since measurement of the same analytes present in chronic infectious and autoimmune liver diseases, where persistent fatigue is also a major symptom, failed to demonstrate the same changes. Further studies of other ME/CFS and overlapping disease cohorts are warranted in future.


Founder of Health Rising and Phoenix Rising
Staff member
That would suggest it's not an autoimmune disease or not necessarily?
This field is so complicated. I don't know if they measured antibodies or if autoimmunity is necessarily associated with increased cytokines. I would think so but even in MS cytokine levels in the blood don't match up well with the disease. It could be that the real cytokine upregulation is in the spinal fluid.

Get Our Free ME/CFS and FM Blog!

New Threads

Forum Tips

Support Our Work



Shopping on For HR

Latest Resources