Th1, Th2 and Th3 cytokine alteration in schizophrenia

BACKGROUND: Several studies have shown that there is an imbalance between T helper 1 (Th1) cytokines and T helper 2 (Th2) cytokines in patients with schizophrenia. The T helper 3 (Th3) cytokine, transforming growth factor beta-1 (TGF-beta1), has been shown to suppress the production of Th1 cytokines. Therefore it is hypothesized that it may play a role in schizophrenia by suppressing overactive Th1 system. METHODS: We recruited 88 schizophrenic patients and 88 matched controls. The basal plasma concentrations of IFN-gamma (Th1), IL-4 (Th2) and TGF-beta1 (Th3) were studied at the time the patients were admitted to the hospital and following 8 weeks of treatment with antipsychotics. RESULTS: The detection rate of plasma IFN-gamma and basal plasma TGF-beta1 level were significantly higher in schizophrenic patients than in controls whereas detection rate of plasma IL-4 was lower in patients. The ratio of Th1/Th2 cytokines (IFN-gamma/IL-4) was higher in schizophrenic patients. Following the neuroleptic treatment, the IFNgamma and TGF-beta1 levels returned to control values, and IL-4 concentration rose above the control value. CONCLUSION: Schizophrenic patients showed higher Th1/Th2 ratio which is attenuated by effective neuroleptic treatment. It is possible that TGF-beta1 plays a role in reducing the activity of Th1 cytokine.     

Cytokine imbalance in the pathophysiology of major depressive disorder

OBJECTIVE: A substantial body of evidence indicates that dysregulation of the immune system is associated with Major Depressive Disorder (MDD). Because most cytokines have pleiotropic effects, we measured various subsets of cytokines to examine the association between immune response and MDD. METHODS: Forty-eight hospitalized MDD patients and 63 normal controls were recruited. We measured in vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4 ratios for both groups. Depressive symptoms were assessed by Hamilton Depression Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant treatment. RESULTS: At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN-gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4 were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1 production were significantly lower than before treatment. CONCLUSION: We suggest that activation of monocytic proinflammatory cytokines, and inhibition of both Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD. TGF-beta1 may be associated with the regulation of monocytic cytokines as well as Th1 and Th2 cytokines in MDD.     

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

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.     

Intracellular monocytic cytokine levels in schizophrenia show an alteration of IL-6

Several 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-α, 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-α, IL-6 and IL-10 were determined. The intracellular concentration of TNF-α, 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.     

Differences in cytokines between non-suicidal patients and suicidal patients in major depression

Several studies have shown that there is an imbalance between pro-inflammatory and anti-inflammatory cytokines in major depressive disorder (MDD). However, little is known about the role of cytokines in suicide. In the present study, amounts of IL-6, IL-2, IFN-gamma, IL-4, and TGF-beta1 produced by mitogen-stimulated whole blood were measured in 36 MDD patients who had recently attempted suicide, 33 non-suicidal MDD patients, and 40 normal controls. The severity of depression symptoms and suicidal behaviors was evaluated using Hamilton's depression rating scale (HDRS), the Lethality Suicide Attempt Rating Scale (LSARS), and the Risk-Rescue Rating (RRR). Non-suicidal MDD patients had significantly higher IL-6 production than suicidal MDD patients and normal controls (p<0.001). Suicidal MDD patients had significantly lower IL-2 compared with non-suicidal patients and normal controls (p<0.001). Both MDD groups, with or without attempted suicide, had significantly lower IFN-gamma and IL-4 and higher TGF-beta1 production. HDRS scores had significant positive correlations with IL-6, IFN-gamma, and the Th1/Th2 ratio and significant negative correlations with IL-4 in non-suicidal depression patients (p<0.005); however, these correlations did not hold true for suicidal patients. Suicidal MDD patients had no significant correlations between the LSARS or RRR scores and cytokine release. Our findings suggest that the immune response has distinct differences between non-suicidal patients and suicidal patients. Non-suicidal MDD may be associated with increased IL-6 production and a Th1/Th2 imbalance with a shift to Th1, while suicidal MDD may be associated with decreased IL-2.     

CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis

We simultaneously measured 16 cytokines/chemokines in cerebrospinal fluid (CSF) from 14 patients with acute disseminated encephalomyelitis (ADEM) and 20 controls using a fluorescent bead-based immunoassay. A variety of cytokines, such as IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, G-CSF and MIP-1beta, were significantly elevated in ADEM. In particular, G-CSF showed a marked 38-fold increase compared to the control mean. Significant positive correlations with inflammatory parameters in CSF, such as cell counts and protein levels, were found for IFN-gamma, IL-6 and IL-8. In contrast, IL-17 produced by activated CD4(+) memory T cells was not increased. The results suggested that various cytokines related to activation of macrophages/microglias and Th(1) and Th(2) cells are upregulated in CSF in ADEM.     

Elevated levels of interleukin-12 and interferon-gamma in patients with human T lymphotropic virus type I-associated myelopathy

The levels of interleukin-12 (IL-12) (p70 heterodimer), total IL-12 (p70 heterodimer plus p40 chains), interferon-gamma (IFN-gamma) as Th1 cytokine, and those of interleukin-4 (IL-4) and interleukin-10 (IL-10) as Th2 cytokines in sera and cerebrospinal fluid (CSF) from 22 patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) were compared with those of 22 patients with other neurological diseases (OND), including nine anti-HTLV-I-seropositive carriers. Both serum IL-12 (total and p70 heterodimer) and CSF IFN-gamma, measured by the enzyme-linked immunosorbent assay (ELISA), were significantly elevated in patients with HAM as compared to the patients with OND, including the anti-HTLV-I-seropositive carriers. Serum IFN-gamma also was significantly elevated in the HAM patients as compared to the controls. There was no significant difference in the CSF levels of IL-12 (total and p70 heterodimer) between the HAM patients and controls, whereas, for the Th2 cytokines IL-4 was detected in the CSF of four anti-HTLV-I-seropositive carriers of the 13 control patients but not in any of the patients with HAM. No significant difference was found in the serum levels of IL-4 and IL-10, nor in the CSF levels of IL-10 in the patients with HAM and in the controls. These findings indicate that in patients with HAM, the immunological balance of helper T lymphocytes between Th1 and Th2 is toward Th1 in the periphery and that Th1-mediated immunological status in the central nervous system is involved in the pathogenesis of HAM.     

Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF

To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.     

Th2 shift in mononeuritis multiplex and increase of Th2 cells in chronic inflammatory demyelinating polyneuropathy: an intracellular cytokine analysis.

To elucidate the T helper 1 (Th1)/T helper 2 (Th2) balance in various inflammatory neuropathies, we measured the ratio of intracellular interferon-gamma (IFN-gamma)-positive to IL-4-positive cells (intracellular IFN-gamma/IL-4 ratio) by flow cytometry in peripheral blood CD4(+) T cells of 14 patients with mononeuritis multiplex (MNM), 12 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 10 patients with Guillain-Barré syndrome (GBS), 23 patients with neurodegenerative disorders and 36 healthy controls by intracellular labeling. The patients with MNM showed a significantly lower intracellular IFN-gamma/IL-4 ratio (P<0.05) and higher IL-4(+)/IFN-gamma(-) cell percentages (P<0.05) than the controls. The increase of IL-4(+)/IFN-gamma(-) cell percentages was especially prominent in MNM of unknown etiology (P<0.005). The patients with CIDP also showed significantly higher IL-4(+)/IFN-gamma(-) cell percentages (P<0.05) than the controls. The IL-4(+)/IFN-gamma(-) cell percentages were increased in some patients with GBS, but the difference was not significant compared with the controls. Thus, our results suggest that a Th2 shift is a characteristic of MNM and may play an important role in the development of the disease.     

In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress.

BACKGROUND: Psychologic stress in humans induces the production of proinflammatory cytokines, such as interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6), and that of the negative immunoregulatory cytokine, IL-10. An imbalance of omega6 to omega3 polyunsaturated fatty acids (PUFAs) in the peripheral blood causes an overproduction of proinflammatory cytokines. The omega3 PUFAs reduce the production of proinflammatory cytokines. METHODS: This study examines whether an imbalance in omega6 to omega3 PUFAs in human blood predicts a greater production of proinflammatory cytokines in response to psychologic stress. Twenty-seven university students had serum sampled a few weeks before and after as well as 1 day before a difficult oral examination. We determined the omega6 and omega3 fractions in serum phospholipids as well as the ex vivo production of IFN-gamma, TNF-alpha, IL-6, IL-10, and IL-5 by diluted whole blood stimulated with polyclonal activators. RESULTS: Academic examination stress significantly increased the ex vivo, stimulated production of IFN-gamma, TNF-alpha and IL-10, and the IFN-gamma/IL-5 production ratio. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had significantly greater stress-induced TNF-alpha and IFN-gamma responses than subjects with higher serum omega3 PUFAs and a lower omega6/omega3 ratio, respectively. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had a significantly higher stress-induced increase in the IFN-gamma/IL-5 ratio than the remaining subjects. CONCLUSIONS: Psychologic stress induces a Th-1-like or proinflammatory response in some subjects. An imbalance in the omega6 to omega3 PUFA ratio appears to predispose humans toward an exaggerated Th-1-like response and an increased production of monocytic cytokines, such as TNF-alpha, in response to psychologic stress. The results suggest that increased omega3 PUFA levels may attenuate the proinflammatory response to psychologic stress.     

Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function

Opiate addiction influences many physiological functions including immune responses. The objective of this study was to investigate the immune system function in heroin addicted patients submitted to methadone or buprenorphine maintenance treatment compared to untreated heroin addicts and healthy controls. Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58+/-12.7 mg/day) or buprenorphine (mean dose 9.3+/-2.3mg/day) since at least 6 months; group D was composed of 15 sex and age matched healthy controls. Lymphoproliferation and peripheral mononuclear cell cultures production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokine TNF-alpha were evaluated in all the patients and controls. PHA-lymphoproliferation was lower in untreated heroin addicts than in controls, while it was normal in methadone and buprenorphine treated patients. An altered Th1/Th2 balance, characterized by reduced IL-4, IFN-gamma and TNF-alpha but normal IL-2 levels, was present in untreated heroin addicted subjects, while the Th1/Th2 balance was well conserved in the methadone and buprenorphine groups. These findings suggest that the immune system abnormalities in heroin addicted patients can be restored to almost normal values by controlled treatment with methadone and buprenorphine.     

IFN-beta1a and IFN-beta1b have different patterns of influence on cytokines

Multiple sclerosis is characterized by elevated levels of proinflammatory cytokines produced by Th1 cells and decreased levels of anti-inflammatory cytokines produced by Th2 cells. IFN-beta treatment shifts the immune response from the Th1 to Th2 pattern, thus enhancing the production of anti-inflammatory Th2 cytokines such as IL-4, IL-10, and decreasing the production of proinflammatory Th1 cytokines such as IFN-gamma. To determine which IFN-beta has the stronger immunomodulatory effect we compared the levels of IL-4, IL-10, and IFN-gamma of 12 relapsing-remiting MS patients treated with IFN-beta1b (Betaferon) with those of 10 patients treated with IFN-beta1a (Avonex). There were no statistically significant differences in duration of disease, number of relapses before and during treatment, and in EDSS after 2 years of treatment. After 1 year of treatment the concentration of IFN-gamma was significantly lower in the Betaferon group, and concentrations of IL-4 and IL-10 were significantly higher in the Avonex group. It appears that IFN-beta1b has a downregulatory effect on both Th1 and Th2 cytokines, while IFN-beta1a causes a shift of the cytokine profile toward the Th2 phenotype. These two IFN have different influences on the pattern of cytokines in MS: IFN-beta1a enhances the production of anti-inflammatory cytokines IL-4 and IL-10 and IFN-beta1b decreases the production of the proinflammatory cytokine IFN-gamma.     

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

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-gamma (IFN-gamma) may be lowered. In a longitudinal design, we studied the production of both IFN-gamma 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-gamma 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-gamma 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 相似文献   

Cytokine secretion profile of myelin basic protein-specific T cells in multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a presumed autoimmune pathogenesis involving autoantigen-specific CD4+ T cells and cytokines. A similar frequency of T cells responding to myelin basic protein (MBP), a putative target in MS, has been observed in MS patients and controls. To dissect the differences between MBP-specific T cells in patients and controls, we have analyzed the cytokine secretion profile of such autoreactive T cells. MBP-specific T cell clones (TCC) were isolated from the peripheral blood of MS patients and controls by limiting dilution. Expression of mRNA for interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) was assessed by polymerase chain reaction whereas secretion of cytokine protein was measured by ELISA. MBP-specific TCC exhibited a heterogeneous cytokine secretion profile with clones displaying Th1, Th2 and Th0 phenotypes. A significant difference in the distribution of the cytokine profile was noted between MS patients and controls. Although the frequency of Th1 secreting MBP-reactive TCC was similar between MS patients and controls, stable MS patients had a significant association with the Th0 phenotype whereas healthy individuals were associated with the Th2 phenotype. In comparison to control TCC, MBP-specific TCC from MS patients secreted increased amounts of IFN-gamma, IL-4 and IL-10 and decreased quantities of TGF-beta. Thus, these studies suggest that there is a dysregulation in the balance between pro-inflammatory Th1 and anti-inflammatory Th2 cytokines in MS. It appears that the presence of Th1 secreting autoreactive T cells in healthy individuals may be counterbalanced by the presence of cells secreting Th2 cytokines and by the augmented production of the immunosuppressive cytokine TGF-beta, whereas in MS there is a decrease in these anti-inflammatory agents.     

Effect of risperidone on serum cytokines

A variety of cytokines are dysregulated in schizophrenia, and some antipsychotic drugs effect cytokines. In order to examine the effect of risperidone on plasma cytokines, we measured the serum level of IL-1b, IL-2, IL-6, IL-12, and INF-g during acute states of illness, and after 4 weeks of treatment with risperidone in 19 schizophrenic patients. The patients' psychopathology was assessed by PANSS. Plasma IL-12 levels increased significantly after 4 weeks of treatment (p = .002). Plasma IL-b, IL-2, IL-6, and INF-g levels were not significantly different before and after treatment. There were no significant correlations between the changes in cytokine levels and the changes in PANSS scores. Increased IL-12 may contribute to activation of immune responses during treatment with risperidone. IL-12 may play an important role in immune responses related to neuropsychiatry.     

Elevated cytokine levels in children with autism spectrum disorder

This study compared production of IL-2, IFN-gamma, IL-4, IL-13, IL-5 and IL-10 in peripheral blood mononuclear cells from 20 children with autism spectrum disorder to those from matched controls. Levels of all Th2 cytokines were significantly higher in cases after incubation in media alone, but the IFN-gamma/IL-13 ratio was not significantly different between cases and controls. Cases had significantly higher IL-13/IL-10 and IFN-gamma/IL-10 than controls. Conclusion: Children with ASD had increased activation of both Th2 and Th1 arms of the adaptive immune response, with a Th2 predominance, and without the compensatory increase in the regulatory cytokine IL-10.     

Abnormalities in serum concentrations of interleukin-2, interferon-alpha and interferon-gamma in schizophrenia not detected.

The hypothesis of an immunological defect in schizophrenia has been supported by reports on abnormal production of interleukin-2 (IL-2) and interferons (IFNs) in schizophrenic patients. In the present study we determined the serum concentrations of IL-2, IFN-alpha and IFN-gamma in 10 first onset, neuroleptic-naive schizophrenics, in 6 pretreated patients who were drug free (1 week to 2 years) at the time of the investigation and in 15 matched healthy controls. No IFN-alpha was detected in schizophrenics' and in control sera. No differences were found in IL-2 and IFN-gamma levels between schizophrenics and controls. Thus the present study failed to support the hypothesis of an immunological abnormality in schizophrenia on the basis of the determination of IL-2 and IFNs serum levels.     

A regulatory role of prolactin, growth hormone, and corticosteroids for human T-cell production of cytokines

The release of the pituitary hormones, prolactin and growth hormone (GH), and of adrenal corticosteroids is subject to a profound regulation by sleep. In addition these hormones are known to be involved in the regulation of the immune response. Here, we examined their role for in vitro production of T-cell cytokines. Specifically, we hypothesized that increased concentrations of prolactin and GH as well as a decrease in cortisol, i.e., hormonal changes characterizing early nocturnal sleep, could be responsible for a shift towards T helper 1 (Th1) cytokines during this time. Whole blood was sampled from 15 healthy humans in the morning after regular sleep and was activated in vitro with ionomycin and two concentrations of phorbol myrestate acetate (PMA, 8 and 25 ng/ml) in the absence or presence of prolactin, prolactin antibody, GH, glucocorticoid receptor (GR) antagonist RU-486, or mineralocorticoid receptor (MR) antagonist spironolactone. Hormones were examined at physiological concentrations. Production of T-cell derived cytokines was measured at the single cell level using multiparametric flow cytometry. Generally, effects were more pronounced after stimulation with 8 rather than 25 ng/ml PMA. The following changes reached significance (p <.05): prolactin (versus prolactin antibody) increased tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) producing CD4+ and CD8+ cells and interleukin-2 (IL-2) producing CD8+ cells. Compared with control, prolactin antibody decreased, whereas GH increased IFN-gamma+CD4+ cells. RU-486 increased TNF-alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. Surprisingly strong effects were found after MR blocking with spironolactone which increased TNF-alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. No effects on IL-4+CD4+ cells were observed, while the IFN-gamma/IL-4 ratio shifted towards Th1 after spironolactone and after RU-486 plus GH. Results suggest that enhanced prolactin and GH concentrations as well as low cortisol levels during early nocturnal sleep synergistically act to enhance Th1 cytokine activity.     

Production of interferon-alpha and gamma by leukocytes from patients with schizophrenia

Production of interferon (IFN)-alpha and -gamma by leukocytes from 34 patients with acute schizophrenia and 34 controls was measured before and after 5-6 weeks of antipsychotic treatment by using Sendai virus as IFN-alpha inducer and lentil lectin as inducer for IFN-gamma production. The schizophrenia series included 13 first admission patients (mean duration of illness 1.1 years) and 21 re-entry patients (mean duration of illness 10.1 years). Of the total series 23 were drug-free at the time of pretreatment sampling. In all subgroups the schizophrenic patients produced less IFNs than healthy controls although the differences reached statistical significance only in the total group of schizophrenic patients with regard to production of IFN-alpha. The antipsychotic drug treatment did not have an effect on IFN production. The techniques used, the influence of genetic factors, and eventual clinical implications are discussed.     

Immune-inflammatory markers in schizophrenia: comparison to normal controls and effects of clozapine

The purpose of this study was to investigate immune-inflammatory markers in schizophrenia and the effects of chronic treatment with clozapine, an atypical antipsychotic agent, on these variables. Toward this end, we measured interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R in the blood of 26 normal controls and 14 schizophrenic patients before and after treatment with clozapine. The sIL-2R and IL-6 levels were significantly higher in younger (<35 years) schizophrenic subjects than in normal controls and older (≥ 35 years) schizophrenic subjects. The sIL-6R levels were significantly lower in schizophrenic subjects than in normal controls. Chronic treatment with clozapine significantly increased the blood concentration of sIL-2R; the increases in the latter were significantly related to the dose of clozapine but not to changes in severity of positive or negative symptoms. We conclude that: (a) schizophrenia in younger people is accompanied by increased IL-6 and sIL-2R secretion; and (b) subchronic treatment with clozapine increases sIL-2R levels. Increased plasma sIL-2R may be one mechanism by which neuroleptics exhibit their immunosuppressive effects.