title: Impaired monocyte activation in schizophrenia.
abstract: An inflammatory process is hypothesized in schizophrenia. Innate immunity, in particular the monocyte/macrophage system, has rarely been studied in this disorder, although alterations in microglia indicate a role for this system. Increased monocyte numbers have repeatedly been described. Toll-like receptors (TLRs) mediate the activation of monocytes. We studied the expression of the toll-like receptors TLR-2, TLR-3 and TLR-4 on CD14(+) monocytes in 31 schizophrenia patients and 31 sex- and age-matched healthy controls. Blood samples were taken and stimulated with either lipopolysaccharides (LPS), to mimic a bacterial infection, or polyI:C, to mimic a viral infection. Moreover, the intracellular concentration of interleukin-1ß (IL-1ß) in CD33(+) monocytes was estimated before and after stimulation. The intracellular concentrations of IL-1ß and the TLR surface markers were analyzed by flow cytometry. Receptor expression of TLR-3 and TLR-4, but not of TLR-2, was significantly higher in the schizophrenia patients. After stimulation, patients showed less increase in the expression of TLR-3 and TLR-4 than controls did. The IL-1ß concentration was significantly lower in patients both before and after stimulation with polyI:C, and there was a trend towards a lower concentration after LPS stimulation. The higher expression of TLR-3 and TLR-4 receptors might compensate for a functional deficit, and the lower intracellular concentrations of IL-1ß might reflect the blunted monocytic function in schizophrenia. The immunological dysfunctions might be associated with a poor clearance of pathogens in schizophrenia, which in turn could lead to a low-grade inflammatory process.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Nussbaumstr. 7, 80336 Munich, Germany. Norbert.Mueller@med.uni-muenchen.de
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Wagner
authors.forename: Daniela
authors.initials: D
authors.lastname: Krause
authors.forename: Elif
authors.initials: E
authors.lastname: Weidinger
authors.forename: Agnes
authors.initials: A
authors.lastname: Wildenauer
authors.forename: Michael
authors.initials: M
authors.lastname: Obermeier
authors.forename: Sandra
authors.initials: S
authors.lastname: Dehning
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gruber
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Schwarz
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D053583:Interleukin-1beta / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D012559:Schizophrenia / Q000097:blood / Q000276:immunology*; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D063268:Sialic Acid Binding Ig-like Lectin 3; D051193:Toll-Like Receptors; D011070:Poly I-C