Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1β production

Abstract

Monocyte activation is consistently reported in patients with schizophrenia (SZ). We aimed to study the ultrastructure of monocytes and monocyte production of IL-1β in drug-free patients with SZ and controls. Monocytes from young (18-30 y.o.) healthy and SZ men in relapse were studied. Electron microscopy and morphometry were applied to estimate areas of monocytes, volume density (Vv), areas, and number of organelles. The production IL-1β by monocytes was estimated by the ELISA method. Group differences were examined using ANCOVA. Pearson's correlation coefficients were used to examine the effects of possible confounding variables. Correlation analyses were applied to detect the relationships between the parameters of monocytes measured and between the parameters measured and the IL-1β production. Area of nucleolus, Vv and area of mitochondria and lysosomes, and the number of lysosomes were significantly increased in patients as compared to controls. Area of mitochondria was correlated significantly with Vv and area of lysosomes, and the number of lysosomes was significantly correlated with area of monocyte and Vv of vacuoles only in the control group. The production of IL-1β by monocytes was higher in patients than in controls (p = 0.01) and was correlated with Vv of lysosomes (r = 0.68, p = 0.04) and area of lysosomes (r = 0.78, p = 0.013). The data provide new evidence for over activation of monocytes in SZ and disturbed metabolic relationships between lysosomes, mitochondria, and vacuoles.

The Neuro-Immune Fingerprint of Major Neuro-Cognitive Psychosis or Deficit Schizophrenia: A Supervised Machine Learning Study

“…Importantly, in the present study we computed a composite score reflecting M1 macrophage activity (including IL-1β and TNF-α and their receptors) and found increased composite scores in MNP as compared with controls. These findings further support the monocyte-T lymphocyte theory and the involvement of M1 macrophages in schizophrenia [1,5,55] and additionally indicate that the same M1 pathways are activated in the most severe phenotype of schizophrenia, namely MNP. Moreover, our data that CCL-11 contributes to the prediction of MNP when coupled with TNF-α, IL-1β and sIL-1RA is in agreement with previous findings that schizophrenia is accompanied by a specific cytokine-chemokine profile with increased levels of CCL-11, sTNFR1 and sTNFR2 [47,56].…”

1Q12 Loci Movement in the Interphase Nucleus Under the Action of ROS Is an Important Component of the Mechanism That Determines Copy Number Variation of Satellite III (1q12) in Health and Schizophrenia

“…Small-sized 1q12 domains translocated to the central nucleus area; the nucleoli occupied a large area and approached the 1q12 region. SZ patients' lymphocytes activation has been repeatedly described in a number of papers (Hirata-Hibi et al, 1982;Kloukina-Pantazidou et al, 2010;Uranova et al, 2017). Some authors have described the nucleolus increase (Uranova et al, 2017).…”

“…SZ patients' lymphocytes activation has been repeatedly described in a number of papers (Hirata-Hibi et al, 1982;Kloukina-Pantazidou et al, 2010;Uranova et al, 2017). Some authors have described the nucleolus increase (Uranova et al, 2017). It may be assumed that in the patients' organism oxidative stress chronically stimulates an AR for reparative, antioxidative, and antiapoptotic systems activation.…”

Abnormalities in the brain–immune system in psychotic disorders: from pathogenesis to prevention

“…Interestingly, there were positive correlations between the production of IL-1β and the volume density of lysosomes (r = 0.78, p = 0.013) and the area of lysosomes (r = 0.68, p = 0.04) in the patients with schizophrenia. Even though the sample size of this study was small, these findings provide new evidence that monocytes are overactivated in schizophrenia and that the metabolic relationship between lysosomes, mitochondria, and vacuoles is disturbed [6]. Together, the results suggest it is likely that monocytes would be suitable biomarker targets for the diagnosis and prognosis of psychotic disorders.…”

“…When activated, monocytes release pro-inflammatory cytokines, including interleukin-1β (IL-1β), in response to stimuli in the brain under various pathological conditions [5]. In this issue, Uranova et al [6] report the ultrastructure of monocytes and the monocyte production of IL-1β in drug-free young patients with schizophrenia (n = 9) and healthy young control subjects (n = 11). The area of the nucleolus, the volume density and areas of mitochondria and lysosomes, and the number of lysosomes were significantly increased in the patients as compared to the controls.…”