CFS/ME -Investigation of NK cells & Cytokines

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From: kelly

Note:

A plus for this study is that it has a little larger cohort

than is typical. The CFS/ME group met the 1994

CDC criteria for CFS/ME and were recruited from

an existing cohort in Queensland and New South

Wales, Australia.

Importantly controls were also recruited from the

same geographic area. 93.8% of patients had

weakness >24 hours after exercise compared with

only 9.5% of controls.

Sixty four percent of patients had been diagnosed

with depression or anxiety as well as 19 percent of

controls.

In both groups, individuals with known autoimmune

disorders, psychosis, epilepsy, diabetes and cardiac

related disorders prior to the onset of CFS/ME like

symptoms were excluded from the study.

These exclusions were also applied to the control

group. There was no specific mention of disease

stage.

The authors state:

*Our investigation is the first study to demonstrate

that NK cytotoxic activity remains consistently

decreased in CFS/ME patients during the course of

the disease. However, other immune parameters,

especially cytokine secretions fluctuate at different

time points and therefore demonstrate

inconsistencies in their distribution pattern during

the course of the disease.*

They also stated that certain viruses can affect NK

receptor signalling thus reducing cytoxic activity and

that an increase in viral load occurs during the

course of CFS/ME, may trigger defective cytotoxic

receptor activations hence resulting in

malfunctioning of NK cytotoxic activity.

They concluded:

*The observation of immune dysregulation made in

this study in relation to CFS/ME patients have been

observed in various immunological diseases.

This suggests the need for further investigations into

the underlining disrupted mechanism of decreases

in cytotoxic activity.

It is important to note that these cytokine profiles

were measured following mitogenic stimulation of

PMBCs, serum measurements of cytokines may

display different results.

Further studies are therefore required to investigate

whether changes in cytokine secretions from

activated PMBCs and/or serum levels are associated

with severity and progression of the complex

clinical presentations in CFS/ME pathology. "

Additional research along these lines can be found

here: http://bit.ly/54rR74

and here: http://bit.ly/IL1B6w

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Longitudinal investigation of natural killer

cells and cytokines in chronic fatigue

syndrome/myalgic encephalomyelitis

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

(CFS/ME) is an etiologically unexplained disorder

characterised by irregularities in various aspects of the

immunological function.

Presently, it is unknown whether these immunological

changes remain consistent over time.

This study investigates Natural Killer (NK) cell cytotoxic

activity, NK cell subsets (CD56brightCD16- and

CD56dimCD16+) and cytokines, over the course of

a12 month period in patients with CFS/ME.

Methods:

The participants in the study comprised 65 (47.2+/-11.5

years) CFS/ME participants and 21 (45.2 +/-9.3 years)

non-fatigued controls.

Flow cytometry protocols were used to assess NK

subsets and NK cytotoxic activity at various time points

that included baseline (T1), 6 (T2) and 12 months (T3).

Cytokine secretions were measured following mitogenic

stimulation of peripheral blood mononuclear cells.

Results:

NK cytotoxic activity was significantly decreased in the

CFS/ME patients at T1, T2 and T3 compared to the

non-fatigued group.

Additionally, in comparison to the non-fatigued controls,

the CFS/ME group had significantly lower numbers of

CD56brightCD16- NK cells at both T1 and T2.

Interestingly, following mitogenic stimulation, cytokine

secretion revealed significant increases in IL-10,

IFN-gamma and TNF-alpha at T1 in the CFS/ME

group.

A significant decrease was observed at T2 in the

CFS/ME group for IL-10 and IL-17A while at T3, IL-2

was increased in the CFS/ME group in comparison to

the non- fatigued controls.

Overall cytotoxic activity was significantly decreased at

T3 compared to T1 and T2.

CD56brightCD16- NK cells were much lower at T2

compared to the T1 and T3.

IL-10 and IL-17A secretion was elevated at T2 in

comparison to the T1 and T3.

Conclusion:

These results confirm decreases in immune function in

CFS/ME patients, suggesting an increased susceptibility

to viral and other infections.

Furthermore NK cytotoxic activity may be a suitable

biomarker for diagnosing CFS/ME as it was consistently

decreased during the course of the 12 months study.

Authors:

Ekua W Brenu, Mieke L van Driel, R Staines,

J Ashton, Sharni L Hardcastle, Keane,

Lotti Tajouri, , B Ramos, Sonya

M Marshall-Gradisnik

Credits/Source: Journal of Translational Medicine 2012

The full study can be found here: http://bit.ly/IL1MyO