Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis

Ekua W Brenu,James Keane,Mieke L Van Driel,Donald R Staines,Sandra B Ramos,Sonya M Marshall-Gradisnik,Kevin J Ashton,Sharni L Hardcastle,Daniel Peterson,Lotti Tajouri

doi:10.1186/1479-5876-10-88

Abstract

BackgroundChronic 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.MethodsThe 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.ResultsNK 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-γ and TNF-α 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 T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to T1 and T3.ConclusionThese 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.

Highlights

Immune responses to infection and inflammation are important aspects of physiological homeostasis
Longitudinal assessment of Natural Killer (NK) cytotoxic activity NK cytotoxic activity, that is, the ability of the NK cells to effectively cause apoptosis of K562 cells was significantly reduced (p < 0.05) in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients compared to the control group
The secretion of IL-2 (A) was significantly increased in the CFS/ME patients at the T3, (B) IL-10 increased at the T1 and dropped significantly at the T2 in the CFS/ME group. (C) IL-17A was reduced at the T1 while (D) IFN-γ and (E) tumour necrosis factor (TNF)-α were increased significantly only at the T1

Summary

Introduction

Immune responses to infection and inflammation are important aspects of physiological homeostasis. This involves constant co-ordinated responses from and between the innate and adaptive immune systems [1,2]. Lymphocyte subsets and cytotoxic activity, have been examined in patients with CFS/ME using serum, plasma or blood samples. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. 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

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