Elevated apoptotic cell population in patients with Chronic Fatigue Syndrome (CFS): the pivotal role of protein kinase RNA

OBJECTIVES: A prominent feature of chronic fatigue syndrome

(CFS) is a disordered immune system. Recent evidence indicates

that induction of apoptosis might be mediated in a

dysregulated immune system by the upregulation of growth

inhibitory cytokines. Therefore, the purpose of this study was

to evaluate the apoptotic cell population, interferon-alpha

(IFN-alpha) and the IFN-induced protein kinase RNA (PKR) gene

transcripts in peripheral blood lymphocytes (PBL) of CFS

individuals, as compared to healthy controls.


METHODS: PBL were isolated from CFS (n = 29) and healthy

control individuals (n = 15) and subjected to quantitative

analysis of apoptotic cell population and cell cycle

progression by flow cytometry. Quantitative competitive

polymerase chain reaction (Q/C PCR) and Western blot analysis

were used to assess the levels of PKR mRNA and protein in

control and CFS individuals. In addition, circulating

IFN-alpha was measured by ELISA assay.

RESULTS: Increased

apoptotic cell population was observed in CFS individuals, as

compared to healthy controls (26.6 +/- 12.9% and 9.9 +/- 4.2%,

respectively). The increased apoptotic subpopulation in CFS

individuals was accompanied by an abnormal cell arrest in the

S phase and the G2/M boundary of the cell cycle as compared to

the control group (8.6 +/- 1.2 to 22.8 +/- 2.4 and 3.6 +/-

0.82 to 24.3 +/- 3.4, respectively). In addition, CFS

individuals exhibited enhanced PKR mRNA and protein levels

(mean basal level 3538 +/- 1050 and 2.7 +/- 0.26,

respectively) as compared to healthy controls (mean basal

level 562 +/- 162 and 0.89 +/- 0.18, respectively). In 50% of

the CFS samples (n = 29) treated with 2-aminopurine (2-AP) (a

potent inhibitor of PKR) the apoptotic population was reduced

by more then 50%.

CONCLUSIONS: PKR-mediated apoptosis in CFS

individuals may contribute to the pathogenesis and the fatigue

symptomatology associated with CFS.

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