Increased tumor necrosis factor-alpha concentrations with interleukin-4 concentrations in exacerbations of schizophrenia.

Department of Psychiatry and Alimentary Pharmabiotic Centre, University College Cork, Ireland.
Psychiatry Research (Impact Factor: 2.68). 10/2008; 160(3):256-62. DOI: 10.1016/j.psychres.2007.11.014
Source: PubMed

ABSTRACT Several studies have indicated that cytokines may be involved in the pathophysiology of schizophrenia. Previous studies, however, have yielded contradictory results; in this study we assess the plasma levels of both T-helper-1 (Th1) and T-helper-2 (Th2) cytokines in patients with acute exacerbations of schizophrenia. Plasma concentrations of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and soluble receptor of interleukin-6 (sIL-6R) were measured with high sensitivity, enzyme-linked immunosorbent assays (ELISA) in patients with acute exacerbations of schizophrenia as compared with healthy controls. Patients with an acute exacerbation of schizophrenia had significantly increased production of TNF-alpha and significantly reduced production of IL-4 as compared with healthy subjects. No significant difference was observed in IL-6, sIL-6R, IL-8 and IL-10. Acute exacerbations of schizophrenia are associated with increased TNF-alpha concentrations (Th1) with concomitantly reduced concentrations of IL-4 (Th2) and a resulting increased TNF-alpha/IL-4 ratio.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Little information about the effects of conjugated linoleic acids (CLAs) on inflammation and immune function in humans is available. This study investigated the effects of CLAs, with and without Vitamin E on immunity and inflammatory parameters in adults with active rheumatoid arthritis (RA). In a double-blind clinical trial, 78 patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months; group C: 2.5 g CLAs, group E: 400 mg Vitamin E, group CE: CLAs plus Vitamin E, group P: Placebo. Cytokines, matrix metalloproteinase 3 (MMP-3) and citrullinated antibody (CCP-A) were measured by ELISA method and Vitamin E by high-performance liquid chromatography. Consider statistical methods there were no significant differences between groups in cytokines interleukin-2 (IL-2), IL-4, tumor necrosis factor-α (TNF-α), IL-1β, IL-2/IL-4, CCP-A white blood cells and neutrophils, lymphocyte, monocytes, and eosinophils numbers. TNF-α decreased in all groups, but its reduction was significant in group CE. IL-1β increased in groups P (P = 0.004) and E (P = 0.041) but the difference between group P and CE was significant. IL-4 decreased in groups C, CE and E (P = 0.03, P = 0.03, P = 0.07 respectively). IL2 did not change significantly within groups. CCP-A increased in groups P (P = 0.035) and E (P = 0.05), while it decreased in groups CE (P = 0.034). CCP-A and MMP-3 decrease were significant between groups P and CE. MMP-3 reduction was significant in group CE. Co-supplementation CLAs and Vitamin E may be effective in the level of inflammatory markers in RA patients.
    International journal of preventive medicine 12/2014; 5(12):1567-77.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N=20) or bipolar disorder (BD=20) compared with healthy controls (HCs, N=20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P=0.03 and P=0.002; P=0.024 and P=0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P=0.01, P=0.001 and P=0.09; SCZ subjects: P=0.02, P=0.05 and P=0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P=0.02) and upregulated il4 (P=0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P=0.006 and P=0.003) and tgfβ (P=0.004 and P=0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.
    07/2014; 4:e406. DOI:10.1038/tp.2014.46
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is substantial interest in the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine in psychiatric research, as it exerts psychotomimetic and antidepressant effects in rodents and humans. Here we investigated proteomic changes in brain and serum after acute treatment of rats with ketamine using two targeted proteomic profiling methods. Multiplex immunoassay profiling of serum identified altered levels of IL-4, TNFα and FGF-9, suggesting a link between ketamine exposure and peripheral inflammation and growth factor dysregulation. Selected reaction monitoring mass spectrometry (SRM-MS) profiling of rat brain tissue found that proteomic changes occurred in the frontal cortex and to a greater extent in the hippocampus. This mainly involved changes in signalling kinases and proteases such as PKCβ, neurochondrin (NCDN), calcineurin (PP2BC), ERK1 and MTOR. Furthermore, altered levels were found for proteins associated with neurotransmitter metabolism (AATM, COMT), synaptic vesicle endo-/exocytosis (NSF, SYN1, PACN1) and consistent with previous global proteomic studies, we confirmed known changes in mitochondrial complex I (NDUFS1), prohibitin (PHB) and neurofilament proteins (NFL, AINX). Taken together, the proteomic changes parallel those described in human psychiatric pathology. The results will help to elucidate ketamine's mechanism of action, which will facilitate development of novel drugs for the treatment of schizophrenia and major depressive disorder.
    Journal of Proteome Research 11/2014; 14(1). DOI:10.1021/pr5009493 · 5.06 Impact Factor