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

Int J Neuropsychopharmacol. 2011 Jul;14(6):746-55. doi: 10.1017/S1461145710001653. Epub 2011 Jan 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism*
  • Interleukin-2 Receptor alpha Subunit / blood
  • Interleukin-2 Receptor alpha Subunit / chemistry
  • Lymphocyte Activation*
  • Macrophage Activation*
  • Male
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Schizophrenia / blood
  • Schizophrenia / immunology*
  • Schizophrenia / metabolism
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism
  • Solubility
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Cytokines
  • IL2RA protein, human
  • Inflammation Mediators
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Messenger
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein