Human endogenous retrovirus HERV-E λ 4-1 in immunopathogenesis of affective disorder

Abstract

The aim of this work was to study a dependence between the production level of some pro-inflammatory cytokines by peripheral blood mononuclear cells, and activation of human endogenous retrovirus HERV-E 4-1 in the patients with recurrent depression. Patients and methods: the study included 30 patients with an verified diagnosis of recurrent depression (F 33.0) aged 26-45 years, with a disease duration of at least 3 months prior to inclusion into the study. Peripheral blood mononuclear cells were isolated by centrifugation in Ficoll density gradient (1.078 g/cm3). The human endogenous retrovirus HERV-E 4-1 env gene expression was determined by polymerase chain reaction using paired oligonucleotide primers. To assess the cytokine production, peripheral blood mononuclear cells were cultured for 24-72 hours, depending on the experimental conditions. Quantitative determination of spontaneous cytokine production was carried out by a sandwich variant of ELISA method in conditioned media from the cell cultures, according to the manufacturer instructions. Results: our data reveal higher production of IL-1 and IFN in peripheral blood mononuclear cells from those patients with recurrent depression who showed detectable HERV-E 4-1 env expression compared to the patients in whom the HERV-E 4-1 env gene expression was not detected. When studying correlation between HERV-E 4-1 env expression and production of IL-1 and IFN, a positive correlation between the studied parameters was established. Thus, taking into account our earlier data on HERV-E 4-1 immunomodulatory properties, as well as literature data concerning the HERV transcripts found in brains of mentally ill patients, along with increase of IL-1 and IFN production in the patients with recurrent depression and positive HERV-E 4-1 env gene expression, and a positive correlation between the HERV-E 4-1 env gene expression and increased level of cytokines involved in formation of pathological events in the nervous system in the patients with depression, one may conclude that activation of HERV-E 4-1 could participate in immunopathogenesis of recurrent depression by stimulating the synthesis of pro-inflammatory cytokines.