Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein Kinase RNA

. Vojdani A, Ghoneum M, Choppa PC, Magtoto L, Lapp CW (Immunosciences Laboratory Inc., Beverly Hills, and Charles Drew University School of Medicine and Science, Los Angeles, California, and the Hunter‐Hopkins Centre, Charlotte, North Carolina, USA). Elevated apoptotic cell population in patients with chronic fatigue syn‐drome: the pivotal role of protein kinase RNA. J Intern Med 1997; 242: 465478. 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‐ a) and the IFN‐induced protein kinase RNA (PKR)gene transcripts in peripheral blood lymphocytes (PBL) of CFS individuals, as compared to healthy controls. Subjects and 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 (QIC PCR) and Western blot analysis were used to assess the levels of PKR mRNA and protein in control and CFS individuals. In addition, circulating IFNα was measured by ELISA assay. Results: Increased apoptotic cell population was observed in CFS individuals, as compared to healthy controls (26.6 2 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 G2lM boundary of the cell cycle as compared to the control group (8.6 ‐I 1.2 to 22.8 2 2.4 and 3.6 5 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 5 162 and 0.89 ‐I 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.