Effects of Clozapine on In Vitro Immune Parameters A Longitudinal Study in Clozapine-Treated Schizophrenic Patients

Hinze-Selch, D.; Becker, E. W.; Stein, Gerburg M.; Berg, Peter A.; Mullington, Janet; Holsboer, Florian; Pollmächer, Thomas

doi:10.1016/s0893-133x(98)00006-2

Cited by 64 publications

(34 citation statements)

References 31 publications

(32 reference statements)

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“…In contrast to other studies [22,23], we observed immunomodulatory effects not only after application of the atypical neuroleptic drug clozapine but also after application of haloperidol. These findings are supported by reports which describe effects of haloperidol and clozapine through an enhanced production of the IL-1 receptor antagonist [12,24] and an inhibited production of IL-1ß and TNF-· [25].…”

Section: Discussioncontrasting

confidence: 99%

The Influence of Typical and Atypical Neuroleptic Drugs in the Production of Interleukin-2 and Interferon-Gamma in vitro

et al. 2002

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Alterations of cytokine levels represent the most consistent finding from studies concerning the involvement of the immune system in the etiology of schizophrenia. These results have been discussed controversially due to the potential influence of drug treatment on cytokine production and on the experimental procedures used for cytokine measurement. In the present study, the influences of typical and atypical neuroleptic drugs (haloperidol and clozapine) as well as a tricyclic antidepressive drug (amitriptyline) on cytokine levels (IL-2 and IFN-γ) were examined in vitro in a whole blood assay under various conditions of phytohemagglutinin (PHA) stimulation and drug incubation. Stimulation was enhanced by haloperidol and clozapine, but not by the antidepressant, meaning that the results of decreased cytokine levels seen in earlier studies in schizophrenic patients cannot be explained through drug influences alone. Furthermore, our findings allow us to conclude that, in contrast to the antidepressant drug, the typical and atypical neuroleptic drugs seem to influence the examined cytokine levels.

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Section: Discussioncontrasting

confidence: 99%

The Influence of Typical and Atypical Neuroleptic Drugs in the Production of Interleukin-2 and Interferon-Gamma in vitro

et al. 2002

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“…In accordance with others (37)(38)(39)(40)(41), indirect immunofluorescence assay and flow cytometry provided evidence that certain components of the IgG fraction from these patients can recognize rat cerebral frontal cortex neural cells. The presence of serum Abs was also detected in neurolepticnaive (42) and neuroleptic-treated schizophrenic patients (43,44).…”

Section: Discussionmentioning

confidence: 92%

Antibodies Against Cerebral M1 Cholinergic Muscarinic Receptor from Schizophrenic Patients: Molecular Interaction

Borda

Rivera

Joensen³

et al. 2002

The Journal of Immunology

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We demonstrated the presence of circulating Abs from schizophrenic patients able to interact with cerebral frontal cortex-activating muscarinic acetylcholine receptors (mAChR). Sera and purified IgG from 21 paranoid schizophrenic and 25 age-matched normal subjects were studied by indirect immunofluorescence, flow cytometry, immunoblotting, dot blot, ELISA, and radioligand competition assays. Rat cerebral frontal cortex membranes and/or a synthetic peptide, with an amino acid sequence identical with that of human M1 mAChR, were used as Ags. By indirect immunofluorescence and flow cytometry procedures, we proved that serum-purified IgG fraction from schizophrenic patients reacted to neural cell surfaces from rat cerebral frontal cortex. The same Abs were able to inhibit the binding of the specific M1 mAChR radioligand [3H]pirenzepine. Immunoblotting experiments showed that IgG from schizophrenic patients revealed a band with a molecular mass coincident to that labeled by an anti-M1 mAChR Ab. Using synthetic peptide for dot blot and ELISA, we demonstrated that these Abs reacted against the second extracellular loop of human cerebral M1 mAChR. Also, the corresponding affinity-purified antipeptide Ab displayed an agonistic-like activity associated to specific receptor activation, increasing cyclic GMP production and inositol phosphate accumulation, and protein kinase C translocation. This paper gave support to the participation of an autoimmune process in schizophrenia.

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“…Although the suppression effect was visible only above a threshold concentration of 1 M, which is hardly reached in clinical treatment, there might still be an effect of long-term application on the immune system. An in vivo immune-suppressive effect of clozapine was recently confirmed by another study, 73 whereas these authors reported an immune stimulation in vitro, in disagreement with the results of Leykin et al 72 In another study, 74 elevated levels of sIL-2R were observed only in patients with schizophrenia who were treated with the atypical neuroleptic compound clozapine. These findings, however, did not stand uncontradicted.…”

Section: Production Of: Il-2 (T1) Il-2 (T2) Il-2 (T3) Ifn-␥ (T1) Ifn-mentioning

confidence: 84%

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

et al. 2000

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A pattern of aberrations in the T-cell cytokine system that is typical for autoimmune disorders has also been reported in patients with schizophrenia, namely a decreased interleukin-2 (IL-2) production and increased levels of the soluble IL-2 receptor (sIL-2R). It has also been reported that the production of interferon-␥ (IFN-␥) may be lowered. In a longitudinal design, we studied the production of both IFN-␥ and IL-2 and their correlation in patients with schizophrenia during treatment and investigated whether associations exist between cytokine production and clinical variables. The production of IFN-␥ and IL-2 was measured in equal numbers (n = 29) of patients with schizophrenia (DSM-IV) and controls who were matched for age and gender. Patients were measured 1 day after admission (T1), after 14 (T2) and 28 (T2) days of treatment. Psychopathology was assessed after these times. The production of both IFN-␥ and IL-2 was significantly lower in patients than in controls throughout the whole investigation period (T1-T3). The productions of both cytokines were significantly correlated in controls (r = 0.60, P Յ 0.001) as well as in patients with schizophrenia (mean production T1-T3: r = 0.71, P Յ 0.001). No associations between cytokine measurements and psychopathology or age-at-onset could be found. Our findings of lowered and correlated IFN-␥ and IL-2 production indicate that alterations in the cytokine system of patients with schizophrenia might resemble those in autoimmune disorders. It is suggested that these immunological abnormalities are associated with acute exacerbation, rather than with a clinical subtype of schizophrenia. Molecular Psychiatry (2000) 5, 150-158.

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Effects of Clozapine on In Vitro Immune Parameters A Longitudinal Study in Clozapine-Treated Schizophrenic Patients

Cited by 64 publications

References 31 publications

The Influence of Typical and Atypical Neuroleptic Drugs in the Production of Interleukin-2 and Interferon-Gamma in vitro

The Influence of Typical and Atypical Neuroleptic Drugs in the Production of Interleukin-2 and Interferon-Gamma in vitro

Antibodies Against Cerebral M1 Cholinergic Muscarinic Receptor from Schizophrenic Patients: Molecular Interaction

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

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