Song C, Lin AH, Kenis G, Bosmans E, Maes M. Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist. Schizophr Res 42: 157-164
ABSTRACT In schizophrenic patients, multiple immune abnormalities have been reported, including increased production of proinflammatory cytokines. There is some evidence that antipsychotic drugs may have immunosuppressive effects. The aim of this study was to examine the in-vitro effects of different concentrations of antipsychotic agents on cytokine production by human whole blood. We examined the effects of clozapine and haloperidol, 10(-4), 10(-6) and 10(-8)M, on the unstimulated and stimulated (lipopolysaccharide+phytohemagglutinin) production of interleukin-6 (IL-6), IL-10, interferon-gamma (IFNgamma), and the IL-1 receptor antagonist (IL-1RA). Clozapine, 10(-6) and 10(-8)M, and haloperidol, 10(-4), 10(-6), and 10(-8)M, significantly increased the unstimulated and stimulated production of IL-1RA. Clozapine 10(-6)M significantly increased the stimulated production of IFNgamma. Clozapine 10(-4)M significantly suppressed the unstimulated production of IL-6 and IL-1RA and the stimulated production of IL-6, IL-10, IFNgamma and IL-1RA. The results suggest that both clozapine and haloperidol, at concentrations within the therapeutic range, may exert immunosuppressive effects through an enhanced production of IL-1RA.
- SourceAvailable from: Yong-Ku Kim
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- "To date, there have been conflicting reports regarding the effects of antipsychotics on cytokine levels, and no antipsychotic has been shown to have consistent anti-inflammatory action (Drzyzga et al., 2006). For example , clozapine and haloperidol significantly suppress the production of IL-2 and IFN-γ in vitro (Leykin et al., 1997; Song et al., 2000) and IL-2 in vivo (Kim et al., 2000). These inconsistent or contradictory effects of antipsychotics on pro-inflammatory cytokines may arise from the aforementioned adverse metabolic effects. "
ABSTRACT: Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GR) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the antioxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GR have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation. Copyright © 2015. Published by Elsevier Inc.Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2015; DOI:10.1016/j.pnpbp.2015.06.008 · 4.03 Impact Factor
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- "There is some evidence that antipsychotic drugs may have immunosuppressive effects. For example, in vitro studies have observed that haloperidol and clozapine decrease cytokine secretion in lymphocytes from both schizophrenia patients and healthy controls (Song et al. 2000). In the current study, patients with chronic schizophrenia were on long-term antipsychotic treatment. "
ABSTRACT: Objective A substantial body of evidence implicates TNF-alpha (TNFα) and TNFα-related signaling pathways in the pathophysiology of schizophrenia. The current study examined the relationship between TNFα serum levels and both psychopathological as well as cognitive symptoms in schizophrenia. Materials and methods Serum TNFα levels were assessed in 89 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum TNFα levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Results TNFα levels were significantly lower in patients with chronic schizophrenia relative to healthy control subjects (pPsychopharmacology 06/2014; 232(1). DOI:10.1007/s00213-014-3650-y · 3.99 Impact Factor
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- "The limitation of this study is that all schizophrenia patients were treated with haloperidol, typical neuroleptic. Haloperidol has been shown to decrease production of many inflammatory cytokines and cytokine receptors or have no effect on their production (Akiyama, 1999; Pollmächer et al., 1997; Leykin et al., 1997; Moots et al., 1999; Song et al., 2000; Kowalski et al., 2001; Szuster- Ciesielska et al., 2004; Zhang et al., 2004, 2009; Romero et al., 2007; Kato et al., 2011). Only in one report increased interleukin- 12 levels after treatment with haloperidol in the first episode psychosis have been detected (Crespo-Facorro et al., 2008). "
ABSTRACT: Altered immune response, including low-grade inflammatory processes, is involved in the pathogenesis of schizophrenia, a chronic psychiatric disorder with complex etiology. Distinct gene variants of a number of pro-inflammatory and chemotactic cytokines together with their receptors associate with this disorder. Interleukin-2 receptor gamma (IL-2RG) represents an important signaling component of many interleukin receptors and so far, no data on the functional state of this receptor in schizophrenia have been reported. The aim of this study was to investigate mRNA expression of the IL2RG gene (IL2RG) in schizophrenia patients in comparison with healthy subjects (controls). Total RNA was isolated from peripheral blood of 66 schizophrenia patients and 99 healthy subjects of Armenian population. The mRNA expression was determined by quantitative real-time polymerase chain reaction (RT-PCR) using PSMB2 as housekeeping gene. IL2RG mRNA expression was upregulated in peripheral blood of patients in comparison with controls (patients vs. controls, median [interquartile range]: 2.080 [3.428-1.046] vs. 0.324 [0.856-0.000], p<0.0001). In conclusion, our findings suggest that over-expression of the IL2RG gene may be implicated in altered immune response in schizophrenia and contribute to the pathomechanisms of this disorder.Psychiatry Research 03/2014; DOI:10.1016/j.psychres.2014.03.020 · 2.68 Impact Factor