Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review.
BACKGROUND
Cytokines play an important role in infection and inflammation and are crucial mediators of the cross-talk between the brain and the immune system. Schizophrenia would be associated with an imbalance in inflammatory cytokines, leading to a decrease in Th1 and an increase in Th2 cytokine secretion. However, data published so far have been inconsistent. The primary objective of the present meta-analysis was to verify whether the cytokine imbalance hypothesis of schizophrenia is substantiated by evidence.


METHODS
Cross-sectional studies were included if they assessed in vivo plasma or serum cytokine concentrations and/or in vitro secretion of cytokines by peripheral blood leukocytes from schizophrenia patients and healthy volunteers.


RESULTS
Data from 62 studies involving a total sample size of 2298 schizophrenia patients and 1858 healthy volunteers remained for analysis. Ten cytokines were assessed, including the prototypic Th1 and Th2 cytokines gamma interferon (IFN-gamma) and interleukin 4 (IL-4) as well as IL-2, soluble IL-2 receptor (sIL-2R), IL-1beta, IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha (TNF-alpha), IL-6, soluble IL-6 receptor (sIL-6R), and IL-10. The results show that an increase occurs in in vivo IL-1RA, sIL-2R, and IL-6 and a decrease occurs in in vitro IL-2 in schizophrenia. No significant effect sizes were obtained for the other cytokines.


CONCLUSIONS
These findings provide the first evidence of establishment of an inflammatory syndrome in schizophrenia, which refutes the current hypothesis of a Th2 slant. Caveats are presented to data interpretation, including the role of stress and the effect of weight gain that develops in schizophrenia.
Potvin
Stéphane
S
Department of Psychiatry, Faculty of Medicine, University of Montreal, Fernand-Seguin Research Center, Louis-H Lafontaine Hospital, Montreal, Quebec, Canada.
Stip
Emmanuel
E
Sepehry
Amir A
AA
Gendron
Alain
A
Bah
Ramatoulaye
R
Kouassi
Edouard
E
D020274:Autoimmune Diseases of the Nervous System / Q000175:diagnosis / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D012016:Reference Values; D012559:Schizophrenia / Q000175:diagnosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D018836:Inflammation Mediators