An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces

Abstract

We recently described a pro-inflammatory gene expression signature in the monocytes of 60% of patients with recent-onset schizophrenia (SCZ). Here we investigated whether the T-cell system is also in a pro-inflammatory state. A detailed fluorescence-activated cell sorting (FACS) analysis, e.g. of CD3+CD25+ T cells, IFN-γ+, IL-4+, IL-17A+ (CD4+) lymphocytes and CD4+CD25highFoxP3+ regulatory T cells, was performed on peripheral blood of 26 patients with recent-onset SCZ (in 19 of whom the inflammatory gene expression signature of the monocyte had been determined) and in age-/gender-matched healthy controls. Various relevant T-cell cytokines, e.g. sCD25, IFN-γ, IL-17A and IL-4, were measured in serum by a multiplex assay. We detected: (a) not only higher percentages of pro-inflammatory-prone monocytes, activated CD3+CD25+ T cells and pro-inflammatory Th17 cells in patients, but also higher percentages of anti-inflammatory CD4+CD25highFoxP3+ regulatory T cells and IL-4+ lymphocytes; (b) that this activated T-cell set point was reflected in significantly raised serum levels of sCD25; (c) that the up-regulation of IL-4+-containing lymphocytes was predominantly found in patients characterized by a monocyte pro-inflammatory set point; and (d) that regulatory T-cell and Th17-cell numbers were higher in patients irrespective of the pro-inflammatory state of the monocytes. Our data do not support the concept that the T-cell system is in a simple pro-inflammatory state in recent-onset SCZ, but do show that the monocyte and T-cell networks are activated and involve both pro- and anti-inflammatory forces. This suggests control within an activated inflammatory system.