ELEVATED APOPTOTIC CELL-POPULATION IN PATIENTS WITH CHRONIC-FATIGUE-SYNDROME - 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 up regulation of growth inhibitory cytokines. Therefore, the purpose of t his study was to evaluate the apoptotic cell population, interferon-al pha (IFN-alpha) and the IFN-induced protein kinase RNA (PKR) gene tran scripts in peripheral blood lymphocytes (PBL) of CFS individuals, as c ompared to healthy controls. Subjects and methods, PBL were isolated f rom CFS (n = 29) and healthy control individuals (n = 15) and subjecte d to quantitative analysis of apoptotic cell population and cell cycle progression by now cytometry. Quantitative competitive polymerase cha in reaction (Q/C PCR) and Western blot analysis were used to assess th e levels of PKR mRNA and protein in control and CFS individuals. In ad dition, circulating IFN-alpha was measured by ELISA assay. Results. In creased apoptotic cell population was observed in CFS individuals, as compared to healthy controls (26.6 +/- 12.9% and 9.9 +/- 4.2%, respect ively). The increased apoptotic subpopulation in CFS individuals was a ccompanied by an abnormal cell arrest in the S phase and the G2/M boun dary of the cell cycle as compared to the control group (8.6 +/- 1.2 t o 22.8 +/- 2.4 and 3.6 +/- 0.82 to 24.3 +/- 3.4, respectively). In add ition, CFS individuals exhibited enhanced PKR mRNA and protein levels (mean basal level 3538 +/- 1050 and 2.7 +/- 0.26, respectively) as com pared to healthy controls (mean basal level 562 +/- 162 and 0.89 +/- 0 .18, respectively). In 50% of the CFS samples (n = 29) treated with a- aminopurine (2-AP) (a potent inhibitor of PKR) the apoptotic populatio n was reduced by more then 50%. Conclusions. PKR-mediated apoptosis in CFS individuals may contribute to the pathogenesis and the fatigue sy mptomatology associated with CFS.