An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces.
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.
Department of Immunology, Erasmus MC, Rotterdam, The Netherlands. r.drexhage@erasmusmc.nl
Roosmarijn C
RC
Drexhage
Thomas A
TA
Hoogenboezem
Dan
D
Cohen
Marjan A
MA
Versnel
Willem A
WA
Nolen
Nico J M
NJ
van Beveren
Hemmo A
HA
Drexhage
D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000737:chemistry; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult; D000099153:Pentraxins
D002097:C-Reactive Protein; D016207:Cytokines; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C508017:IL2RA protein, human