1Psychiatry Res 2012 Aug 198: 341-6
PMID22429483
TitleImpaired monocyte activation in schizophrenia.
AbstractAn 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-1 (IL-1) in CD33(+) monocytes was estimated before and after stimulation. The intracellular concentrations of IL-1 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-1 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-1 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.
SCZ Keywordsschizophrenia, schizophrenic
2Eur Arch Psychiatry Clin Neurosci 2012 Aug 262: 393-401
PMID22271344
TitleIntracellular monocytic cytokine levels in schizophrenia show an alteration of IL-6.
AbstractSeveral studies have shown an involvement of the immune system, in particular the monocytic system, in the pathophysiology of schizophrenia. Beside others, the monocyte-derived cytokines TNF-?, IL-6 and IL-10 were found to be affected. Since cytokines are secreted by several different cell types, the cellular source is only clear if intracellular levels are measured. Thus, in order to study the monocytic system in schizophrenia, the intracellular levels of TNF-?, IL-6 and IL-10 were determined. The intracellular concentration of TNF-?, IL-6 and IL-10 in CD33 positive monocytes was evaluated in schizophrenic patients and controls with monoclonal antibodies against these cytokines. In addition, in vitro stimulation with lipopolysaccharide (LPS) or poly I/C, which mimic a bacterial and viral infection, was performed before immunocytochemistry. At baseline, monocytic IL-6 levels were significantly lower in schizophrenic patients than in controls. After stimulation with LPS, compared with baseline, monocytic intracellular IL-6 production tended to increase more in schizophrenic patients. The present results provide further support for the hypothesis of an involvement of a dysfunction of the monocytic system in the pathophysiology of schizophrenia and indicate that especially the pro-inflammatory immune response seems to be impaired.
SCZ Keywordsschizophrenia, schizophrenic
3Eur Arch Psychiatry Clin Neurosci 2012 Aug 262: 393-401
PMID22271344
TitleIntracellular monocytic cytokine levels in schizophrenia show an alteration of IL-6.
AbstractSeveral studies have shown an involvement of the immune system, in particular the monocytic system, in the pathophysiology of schizophrenia. Beside others, the monocyte-derived cytokines TNF-?, IL-6 and IL-10 were found to be affected. Since cytokines are secreted by several different cell types, the cellular source is only clear if intracellular levels are measured. Thus, in order to study the monocytic system in schizophrenia, the intracellular levels of TNF-?, IL-6 and IL-10 were determined. The intracellular concentration of TNF-?, IL-6 and IL-10 in CD33 positive monocytes was evaluated in schizophrenic patients and controls with monoclonal antibodies against these cytokines. In addition, in vitro stimulation with lipopolysaccharide (LPS) or poly I/C, which mimic a bacterial and viral infection, was performed before immunocytochemistry. At baseline, monocytic IL-6 levels were significantly lower in schizophrenic patients than in controls. After stimulation with LPS, compared with baseline, monocytic intracellular IL-6 production tended to increase more in schizophrenic patients. The present results provide further support for the hypothesis of an involvement of a dysfunction of the monocytic system in the pathophysiology of schizophrenia and indicate that especially the pro-inflammatory immune response seems to be impaired.
SCZ Keywordsschizophrenia, schizophrenic