interleukin-8 and Schizophrenia

Immune system dysfunction is considered to play an aetiological role in schizophrenia spectrum disorders, with substantial alterations in the concentrations of specific peripheral inflammatory proteins, such as cytokines. However, there are inconsistencies in the literature over which inflammatory proteins are altered throughout the course of illness. Through conducting a systematic review and network meta-analysis, this study aimed to investigate the patterns of alteration that peripheral inflammatory proteins undergo in both acute and chronic stages of schizophrenia spectrum disorders, relative to a healthy control population.. In this systematic review and meta-analysis, we searched PubMed, PsycINFO, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to March 31, 2022, for published studies reporting peripheral inflammatory protein concentrations in cases of people with schizophrenia-spectrum disorders and healthy controls. Inclusion criteria were: (1) observational or experimental design; (2) a population consisting of adults diagnosed with schizophrenia-spectrum disorders with a specified indicator of acute or chronic stage of illness; (3) a comparable healthy control population without mental illness; (4) a study outcome measuring the peripheral protein concentration of a cytokine, associated inflammatory marker, or C-reactive protein. We excluded studies that did not measure cytokine proteins or associated biomarkers in blood. Mean and SDs of inflammatory marker concentrations were extracted directly from full-text publshed articles; articles that did not report data as results or supplementary results were excluded (ie, authors were not contacted) and grey literature and unpublished studies were not sought. Pairwise and network meta-analyses were done to measure the standardised mean difference in peripheral protein concentrations between three groups: individuals with acute schizophrenia-spectrum disorder, individuals with chronic schizophrenia-spectrum disorder, and healthy controls. This protocol was registered on PROSPERO, CRD42022320305.. Of 13 617 records identified in the database searches, 4492 duplicates were removed, 9125 were screened for eligibility, 8560 were excluded after title and abstract screening, and three were excluded due to limited access to the full-text article. 324 full-text articles were then excluded due to inappropriate outcomes, mixed or undefined schizophrenia cohorts, or duplicate study populations, five were removed due to concerns over data integrity, and 215 studies were included in the meta-analysis. 24 921 participants were included, with 13 952 adult cases of schizophrenia-spectrum disorder and 10 969 adult healthy controls (descriptive data for the entire cohort were not available for age, numbers of males and females, and ethnicity). Concentration of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and C-reactive protein were consistently elevated in both individuals with acute schizophrenia-spectrum disorder and chronic schizophrenia-spectrum disorder, relative to healthy controls. IL-2 and interferon (IFN)-γ were significantly elevated in acute schizophrenia-spectrum disorder, while IL-4, IL-12, and IFN-γ were significantly decreased in chronic schizophrenia-spectrum disorder. Sensitivity and meta-regression analyses revealed that study quality and a majority of the evaluated methodological, demographic, and diagnostic factors had no significant impact on the observed results for most of the inflammatory markers. Specific exceptions to this included: methodological factors of assay source (for IL-2 and IL-8), assay validity (for IL-1β), and study quality (for transforming growth factor-β1); demographic factors of age (for IFN-γ, IL-4, and IL-12), sex (for IFN-γ and IL-12), smoking (for IL-4), and BMI (for IL-4); and diagnostic factors including diagnostic composition of schizophrenia-spectrum cohort (for IL-1β IL-2, IL-6, and TNF-α), antipsychotic-free cases (for IL-4 and IL-1RA), illness duration (for IL-4), symptom severity (for IL-4), and subgroup composition (for IL-4).. Results suggest that people with schizophrenia-spectrum disorders have a baseline level of inflammatory protein alteration throughout the illness, as reflected by consistently elevated pro-inflammatory proteins, hypothesised here as trait markers (eg, IL-6), while those with acute psychotic illness might have superimposed immune activity with increased concentrations of hypothesised state markers (eg, IFN-γ). Further research is required to determine whether these peripheral alterations are reflected within the central nervous system. This research facilitates an entry point in understanding how clinically relevant inflammatory biomarkers might one day be useful to the diagnosis and prognostication of schizophrenia-spectrum disorders.. None.

Topics: Adult; Biomarkers; C-Reactive Protein; Cytokines; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-12; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Male; Network Meta-Analysis; Schizophrenia; Tumor Necrosis Factor-alpha

Low grade neuroinflammation has been suggested as one of the underlying mechanisms of many psychiatric diseases as well as cognitive disorders. Interleukin 8 (IL-8), a proinflammatory cytokine produced by many cell types including macrophage and microglia, mainly functions as a neutrophil chemoattractant in the bloodstream. IL-8 is also found in the brain, where it is released from microglia in response to proinflammatory stimuli. In this review, we highlight studies focusing on the role of IL-8 in psychiatric diseases such as major depression, bipolar disorder, schizophrenia, sleep disorder, autism spectrum disorder, anxiety disorders and dementia. Increased peripheral IL-8 levels have been reported in these diseases, particularly in schizophrenic disorder, bipolar disorder, obstructive sleep apnea and autism spectrum disorder. The literature on IL-8 and major depression is inconsistent. IL-8 has been found to be a factor associated with schizophrenic prognosis and therapeutic response, and may affect a wide range of symptomatology. Considering that the exact role of immune alterations is still under research, the success of immune-based therapies in psychiatric diseases is limited for the time being.

Topics: Animals; Anxiety Disorders; Depression; Humans; Immunotherapy; Inflammation Mediators; Interleukin-8; Mental Disorders; Neuroinflammatory Diseases; Schizophrenia; Sleep Wake Disorders

Immune parameters are elevated in psychosis, but it is unclear whether alterations are homogenous across patients or heterogeneity exists, consistent with the hypothesis that immune alterations are specific to a subgroup of patients. To address this, we examine whether antipsychotic-naïve first-episode psychosis patients exhibit greater variability in blood cytokines, C-reactive protein, and white cell counts compared with controls, and if group mean differences persist after adjusting for skewed data and potential confounds. Databases were searched for studies reporting levels of peripheral immune parameters. Means and variances were extracted and analyzed using multivariate meta-analysis of mean and variability of differences. Outcomes were (1) variability in patients relative to controls, indexed by variability ratio (VR) and coefficient of variation ratio (CVR); (2) mean differences indexed by Hedges g; (3) Modal distribution of raw immune parameter data using Hartigan's unimodality dip test. Thirty-five studies reporting on 1263 patients and 1470 controls were included. Variability of interleukin-6 (IL6) (VR = 0.19), tumor necrosis factor-α (TNFα) (VR = 0.36), interleukin-1β (VR = 0.35), interleukin-4 (VR = 0.55), and interleukin-8 (VR = 0.28) was reduced in patients. Results persisted for IL6 and IL8 after mean-scaling. Ninety-four percent and one hundred percent of raw data were unimodally distributed in psychosis and controls, respectively. Mean levels of IL6 (g = 0.62), TNFα (g = 0.56), interferon-γ (IFNγ) (g = 0.32), transforming growth factor-β (g = 0.53), and interleukin-17 (IL17) (g = 0.48) were elevated in psychosis. Sensitivity analyses indicated this is unlikely explained by confounders for IL6, IFNγ, and IL17. These findings show elevated cytokines in psychosis after accounting for confounds, and that the hypothesis of an immune subgroup is not supported by the variability or modal distribution.

Topics: C-Reactive Protein; Case-Control Studies; Cytokines; Humans; Interferon-gamma; Interleukin-17; Interleukin-1beta; Interleukin-4; Interleukin-6; Interleukin-8; Leukocyte Count; Lymphocyte Count; Models, Statistical; Prodromal Symptoms; Psychotic Disorders; Schizophrenia; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Many studies have indicated that immune cytokines may be involved in the pathophysiology of schizophrenia. Recently, there have been reports that typical and atypical antipsychotic drugs may influence the levels of cytokines or cytokine receptors. The aim of this study was to compare the effect of typical and atypical antipsychotic drugs on serum interleukin-2 (IL-2), interleukin-6 (IL-6), and interleukin-8 (IL-8) and to investigate the relationship between the changes in cytokines and the therapeutic outcome in schizophrenia.. From April 1996 to August 1997, seventy-eight inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol. Clinical efficacy was determined using the Positive and Negative Syndrome Scale. Serum IL-2 was assayed by radioimmunometric assay, and serum IL-6 and IL-8 concentrations were measured by quantitative enzyme-linked immunosorbent assay in patients and 30 sex- and age-matched normal subjects.. Both risperidone and haloperidol reduced the elevated serum IL-2 concentrations in schizophrenia, and no significant difference was noted in the reduction of serum IL-2 concentrations between risperidone and haloperidol treatment. Neither risperidone nor haloperidol showed significant influence on the higher serum IL-6 or IL-8 concentrations in schizophrenia. Correlations between serum IL-2 or IL-8 concentrations at baseline and the therapeutic outcome were observed, demonstrating that patients presenting with low concentrations of serum IL-2 or IL-8 at baseline showed greater improvement and patients presenting with higher serum IL-2 or IL-8 concentrations at baseline showed less improvement after treatment.. Both typical and atypical anti-psychotic drugs may at least partially normalize abnormal immune alterations in schizophrenia. Some immune parameters at baseline may be useful for predicting the neuroleptic response of schizophrenic patients.

Topics: Adult; Antipsychotic Agents; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Haloperidol; Hospitalization; Humans; Immunity, Cellular; Interleukin-2; Interleukin-6; Interleukin-8; Male; Radioimmunoassay; Risperidone; Schizophrenia; Treatment Outcome

Considering Acute and Transient psychotic disorders (ATPDs) to be a close entity to Schizophrenia (SZ) with a completely different course and outcome, studies evaluating the immunological abnormalities are scarce in ATPDs. We analysed immune-mediated inflammatory marker levels [Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-17 (IL-17) and Tumour necrosis factor-alpha (TNF-α)] in patients with ATPDs (in the acute phase and after remission), and compared these with patients with SZ in remission and with healthy controls.. Ninteen subjects with ATPDs in acute phase of illness were age-/gender-matched with healthy controls and patients with schizophrenia in remission; recruited through purposive sampling. Clinical assessment and immune-marker levels were carried out in all the three groups. Follow -up repeat immune-marker levels assessment in the ATPD group was conducted after remission status was ensured. Immune-marker levels were compared across the three groups.. Patients with ATPDs had elevated levels of the pro-inflammatory cytokines IL-6 and IL-17 and low levels of IL-8 in the acute phase and low levels of IL-6 and elevated levels of IL-8 during the remission phase. Compared to patients with SZ in remission, patients with ATPD in remission had low levels of all the three pro-inflammatory cytokines (with significantly low IL-6 levels and non-significant, yet low levels of IL-8 and IL-17) and had significantly low and high levels of IL-6 and IL-8 respectively than healthy controls.. These findings suggest that there existed immunological abnormalities in the acute and remission phase of illness in patients with ATPDs compared to both patients with SZ in remission and healthy controls.

Topics: Biomarkers; Cytokines; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Psychotic Disorders; Schizophrenia

Transcript levels of cytokines and SERPINA3 have been used to define a substantial subset (40%) of individuals with schizophrenia with elevated inflammation and worse neuropathology in the dorsolateral prefrontal cortex (DLPFC). In this study, we tested if inflammatory proteins are likewise related to high and low inflammatory states in the human DLFPC in people with schizophrenia and controls. Levels of inflammatory cytokines (IL6, IL1β, IL18, IL8) and a macrophage marker (CD163 protein) were measured in brains obtained from the National Institute of Mental Health (NIMH) (N = 92). First, we tested for diagnostic differences in protein levels overall, then we determined the percentage of individuals that could be defined as "high" inflammation using protein levels. IL-18 was the only cytokine to show increased expression in schizophrenia compared to controls overall. Interestingly, two-step recursive clustering analysis showed that IL6, IL18, and CD163 protein levels could be used as predictors of "high and low" inflammatory subgroups. By this model, a significantly greater proportion of schizophrenia cases (18/32; 56.25%; SCZ) were identified as belonging to the high inflammatory (HI) subgroup compared to control cases (18/60; 30%; CTRL) [χ

Topics: Cytokines; Humans; Inflammation; Interleukin-18; Interleukin-6; Interleukin-8; Macrophages; Microglia; Schizophrenia; Tumor Necrosis Factor-alpha

Glutamate and increased inflammation have been separately implicated in the pathophysiology of schizophrenia and the extent of clinical response to antipsychotic treatment. Despite the mechanistic links between pro-inflammatory and glutamatergic pathways, the relationships between peripheral inflammatory markers and brain glutamate in schizophrenia have not yet been investigated. In this study, we tested the hypothesis that peripheral levels of pro-inflammatory cytokines would be positively associated with brain glutamate levels in schizophrenia. Secondary analyses determined whether this relationship differed according to antipsychotic treatment response. The sample consisted of 79 patients with schizophrenia, of whom 40 were rated as antipsychotic responders and 39 as antipsychotic non-responders. Brain glutamate levels were assessed in the anterior cingulate cortex (ACC) and caudate using proton magnetic resonance spectroscopy (

Topics: Antipsychotic Agents; Brain; Encephalitis; Glutamic Acid; Humans; Inflammation; Interleukin-8; Schizophrenia

Immune system dysfunction is hypothesised to contribute to structural brain changes through aberrant synaptic pruning in schizophrenia. However, evidence is mixed and there is a lack of evidence of inflammation and its effect on grey matter volume (GMV) in patients. We hypothesised that inflammatory subgroups can be identified and that the subgroups will show distinct neuroanatomical and neurocognitive profiles.. The total sample consisted of 1067 participants (chronic patients with schizophrenia n = 467 and healthy controls (HCs) n = 600) from the Australia Schizophrenia Research Bank (ASRB) dataset, together with 218 recent-onset patients with schizophrenia from the external Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin) dataset. HYDRA (HeterogeneitY through DiscRiminant Analysis) was used to separate schizophrenia from HC and define disease-related subgroups based on inflammatory markers. Voxel-based morphometry and inferential statistics were used to explore GMV alterations and neurocognitive deficits in these subgroups.. An optimal clustering solution revealed five main schizophrenia groups separable from HC: Low Inflammation, Elevated CRP, Elevated IL-6/IL-8, Elevated IFN-γ, and Elevated IL-10 with an adjusted Rand index of 0.573. When compared with the healthy controls, the IL-6/IL-8 cluster showed the most widespread, including the anterior cingulate, GMV reduction. The IFN-γ inflammation cluster showed the least GMV reduction and impairment of cognitive performance. The CRP and the Low Inflammation clusters dominated in the younger external dataset.. Inflammation in schizophrenia may not be merely a case of low vs high, but rather there are pluripotent, heterogeneous mechanisms at play which could be reliably identified based on accessible, peripheral measures. This could inform the successful development of targeted interventions.

Topics: Brain; Gray Matter; Humans; Interleukin-6; Interleukin-8; Magnetic Resonance Imaging; Schizophrenia; Supervised Machine Learning

Nuclear distribution element like-1 (Ndel1) is a cytosolic oligopeptidase, which was suggested as a potential biomarker of aberrant neurodevelopment and early stage of schizophrenia (SCZ). The involvement of Ndel1 in neurite outgrowth, neuronal migration and neurodevelopment was demonstrated. Moreover, Ndel1 cleaves neuropeptides, including the endogenous antipsychotic peptide neurotensin, and lower Ndel1 activity was reported in SCZ patients compared with healthy controls (HCs). Changes in brain-derived neurotrophic factor (BDNF) and inflammatory cytokines levels were also implicated in SCZ.. This preliminary study aimed to investigate the interactions between these immune and neurodevelopmental/neurotrophic biomarkers, namely BDNF and the recently identified SCZ biomarker Ndel1.. We observed. Although this hypothesis needs to be further explored for a better understanding of the mechanisms by which these altered pathways are associated to each other in SCZ, we suggest that Ndel1 and the inflammatory marker IL-4 are directly correlated.

Topics: Antipsychotic Agents; Biomarkers; Brain-Derived Neurotrophic Factor; Cytokines; Humans; Interleukin-10; Interleukin-17; Interleukin-2; Interleukin-4; Interleukin-8; Neuropeptides; Neurotensin; Peptides; Schizophrenia

Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1β, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1β, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1β, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.

Topics: Biomarkers; Cognition; Female; Humans; Interleukin-6; Interleukin-8; Male; Schizophrenia

The interaction between psychological stress and immune system may be associated with the cognitive impairment of schizophrenia. To employ machine learning algorithms to examine patterns of stress-immune networks with cognitive impairment in chronic schizophrenia, we selected cortisol, tumor necrosis factor (TNF) - α, interleukin (IL) - 2, IL-6 and IL-8 as biochemical indices reflecting the dysfunctional response to psychological stress and immune system in patients with schizophrenia. Basedon 14 kinds of interactions of above five variables, we were able to classify 37 chronic schizophrenia patients and 35 age and gender-matched healthy controls by using decision tree (DT) (Accuracy = 93.1%, Sensitivity = 97.3%, Specificity = 88.6%), random forest (RF) (Accuracy = 94.4%, Sensitivity = 91.9%, Specificity = 97.1%) and support vector machines (SVM) (Accuracy = 98.6%, Sensitivity = 100.0%, Specificity = 97.1%), which indicating that cortisol × TNF-α × IL-8 was the top risk factor for identifying chronic schizophrenia. Furthermore, we found that cortisol × TNF-α × IL-8 was positively correlated with PANSS cognitive subscore. Multiple stepwise linear regression analysis confirmed that PANSS cognitive subscore was correlated with duration of illness and cortisol × TNF-α × IL-8. The results suggest that the glucocorticoid-immune relationship may have an effect on the cognitive impairment of patients.

Topics: Adult; Biomarkers; Cognitive Dysfunction; Female; Humans; Hydrocortisone; Interleukin-8; Male; Mass Screening; Mental Status and Dementia Tests; Middle Aged; Schizophrenia; Schizophrenic Psychology; Stress, Psychological; Support Vector Machine; Tumor Necrosis Factor-alpha

Increasing evidence indicates that oxidative damage and inflammation is present in patients with schizophrenia. In this study, we investigated the association between the serum concentrations of four typical oxidative stress and inflammatory biomarkers (monocyte chemotactic protein-1, heme oxygenase-1, interleukin-8, and 8-Hydroxydeoxyguanine) and schizophrenia using a case-control study design. In total, 44 patients with schizophrenia and 45 normal controls from Shandong Province, China were recruited. Fasting blood samples were collected from all participants and the serum concentration of the four biomarkers were analyzed by Enzyme-linked immunosorbent assay. The concentrations of monocyte chemotactic protein-1 and interleukin-8 were significantly higher in the patients than in the controls, while there was no significant difference in the serum concentrations of heme oxygenase-1 and 8-Hydroxydeoxyguanine. Moreover, the serum concentrations of monocyte chemotactic protein-1 and interleukin-8 in patients were positively correlated with severity of clinical symptoms. Dose-response relationships between serum biomarker concentrations and schizophrenia were observed. This study suggests that levels of monocyte chemotactic protein-1 and interleukin-8 are increased in patients with schizophrenia and correlated with positive symptom severity.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Chemokine CCL2; China; Enzyme-Linked Immunosorbent Assay; Female; Heme Oxygenase-1; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Oxidative Stress; Pilot Projects; Schizophrenia

The relevance of Interleukin-8 (IL-8) cytokine alteration in the peripheral and central system has been widely shown in psychosis while variation in the IL-8 gene remains largely unexplored and to the best of our knowledge, IL-8 polymorphisms have never been specifically targeted in Schizophrenia (Scz). Thus, we set out to search a potential correlation between rs4073, rs2227306 and rs1126647 polymorphisms in IL-8 gene and the development of Scz in a sample of the Tunisian population in a candidate gene approach. Targeted polymorphisms were analysed in 206 patients and 195 controls using PCR-RFLP method. Among all analysed polymorphisms, only rs1126647 showed a significant risk for Scz. After stratification analysis, we noted a significant association of TT genotype and T allele at rs1126647 with paranoid form, and more specifically with female sex. We find that the rare haplotypes at rs4073-rs2227306-rs1126647 of TTT, ACT and TCT, each containing the risk allele rs1126647T, were associated with increased risk for paranoid Scz while only the TCT combination constituted a risk factor for Scz more generally. Our findings support that IL-8 gene may be involved in susceptibility to Scz but this still preliminary and needs to be strengthened by further independent analyses.

Topics: Adult; Alleles; Case-Control Studies; Female; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; Humans; Interleukin-8; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Schizophrenia; Tunisia; Young Adult

Multiple lines of evidence indicate that patients with chronic schizophrenia (SCZ) display executive dysfunction across the illness course. However, the potential molecular pathophysiologic mechanisms remain poorly elucidated. Neurodevelopmental changes caused by alterations of inflammatory mediators and neurotrophins have been shown to occur in the earliest stages of SCZ, and be associated with executive dysfunction (ED) in SCZ. Therefore, the current study was to investigate whether the interplay between BDNF and inflammatory mediators was involved in the disruption of executive function of long-term hospitalized patients with chronic SCZ. Serum cytokines and BDNF levels were measured in 112 long-term hospitalized patients with chronic SCZ and 44 healthy normal controls. Executive functions were assessed by verbal fluency tests (VFT), the Stroop word-color test (Stroop), and the Wisconsin card sorting tests (WCST).The results showed that the patients had higher IL-2, IL-6, IL-8, but lower TNF-α and BDNF compared to control subjects. In the patient group, BDNF was positively associated with IL-2 and IL-8 levels, while lower BDNF levels were correlated with ED measured by VFT and WCST tests. Multiple stepwise regression analyses confirmed that BDNF × IL-8 and BDNF × TNF-α were factors influencing the total score of VFT, while BDNF × IL-8 and BDNF × TNF-α were recognized as influencing factors for WCST scores. Our results suggest complex interactions between BDNF and cytokines were involved in the pathophysiology of executive function impairments in patients with SCZ.

Topics: Adult; Brain-Derived Neurotrophic Factor; Cytokines; Executive Function; Female; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Neuropsychological Tests; Schizophrenia; Tumor Necrosis Factor-alpha

Several observations indicate that cytokine concentrations might also relate to the severity of the psychosis. In this study we assessed whether inflammatory and anti-inflammatory cytokine concentrations are associated with the degree of the psychotic manifestations. A group of 41 patients with schizophrenia suffering from an acute psychosis leading to hospitalization in a psychiatric ward were assessed for the intensity of their psychotic manifestations by the PANSS score. Serum IL-2R, IL-6, IL-8, IL-10 were analyzed by commercial ELISA kits. These patients were compared to controls without schizophrenia. At the univariate analysis, statistically significant elevated levels of the cytokines IL-6, IL-2R and IL-8 were detected in the sera of the patients with schizophrenia compared to controls. At the multivariate analysis, statistically significance held only for IL-2R concentration. Furthermore, positive correlation was found between symptom severity as measured by the PANSS and IL-6 levels as well as IL-2R levels. In Conclusion, our data indicate that elevated serum concentrations of IL-6, IL-8 and IL-2R are associated with severe clinical symptoms measured by the total, general, negative and positive scores of the PANSS scale.

Topics: Adolescent; Adult; Aged; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Psychotic Disorders; Receptors, Interleukin-2; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Young Adult

Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins. Ratings of psychotic symptoms and personality traits were made using the Scales for Assessment of Negative and Positive symptoms, the Structured Clinical Interview for DSM-IV - Axis II Disorders, and the Schizotypal Personality Questionnaire - Brief. A total score for psychotic symptoms and personality traits was constructed for analysis. CSF KYNA was associated with the score for psychotic symptom and personality traits. TNF-α and IL-8 were associated, and the intra-pair differences scores of TNF-α and IL-8 were highly correlated. Intraclass correlations indicated genetic influences on CSF KYNA, TRP, IL-8 and TNF-α. The association between KYNA and psychotic symptoms further supports a role of KYNA in psychotic disorders.

Topics: Bipolar Disorder; Female; Humans; Interleukin-6; Interleukin-8; Kynurenic Acid; Male; Middle Aged; Personality; Psychotic Disorders; Quinolinic Acid; Schizophrenia; Schizophrenic Psychology; Tryptophan; Tumor Necrosis Factor-alpha; Twins

Brain-derived neurotrophic factor (BDNF) interacts with cytokines. Although both BDNF and cytokines occur at abnormal levels in schizophrenia patients, their interactions have not yet been examined. We therefore compared serum BDNF, TNF-α, interleukin (IL)-2, IL-6, and IL-8 levels in 92 chronically medicated schizophrenia patients and 60 healthy controls. We correlated these serum levels within these subject groups with each other and with clinical symptoms assessed according to the Positive and Negative Syndrome Scale (PANSS). Compared to the control group, the schizophrenia patients had significantly lower BDNF and TNF-α levels, and higher IL-2, IL-6, and IL-8 levels. The patients also showed a significant positive correlation between BDNF and both IL-2 and IL-8 levels, and low BDNF and TNF-α levels together were associated with poor performance on the PANSS cognitive factor. Thus, an interaction between cytokines and neurotrophic factors may be implicated in the pathophysiology of chronic schizophrenia. In particular, the cytokine TNF-α may interact with BNDF causing cognitive impairment.

Topics: Adult; Antipsychotic Agents; Brain-Derived Neurotrophic Factor; Cytokines; Female; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Schizophrenia; Tumor Necrosis Factor-alpha

Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD.. Claudin (. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.

Topics: Adolescent; Adult; Autism Spectrum Disorder; Biopsy; Blood-Brain Barrier; Calcium-Binding Proteins; Case-Control Studies; Cerebellum; Cerebral Cortex; Child; Child, Preschool; Claudin-3; Claudin-5; Claudins; DNA-Binding Proteins; Duodenum; Female; Gene Expression; Humans; Interleukin-1beta; Interleukin-8; Male; MARVEL Domain Containing 2 Protein; Matrix Metalloproteinase 9; Microfilament Proteins; Middle Aged; Permeability; Schizophrenia; Tight Junctions

Research suggests that maternal immune activation (MIA) during pregnancy increases the risk of neurodevelopmental disorders including schizophrenia and autism in the offspring. Current theories suggest that inflammatory mediators including cytokines and chemokines may underlie the increased risk of these disorders in humans. For example, elevated maternal interleukin-8 (IL-8) during pregnancy is associated with increased risk of schizophrenia in the offspring. Given this association, the present experiments examined ELR-CXC chemokines CXCL1 and CXCL2, rodent homologues of human IL-8, and activation of their receptors (CXCR1 and CXCR2) in an established rodent model of MIA. Pregnant Long Evans rats were treated with the viral mimetic polyinosinic-polycytidylic acid (polyI:C; 4 mg/kg, i.v.) on gestational day 15. Protein analysis using multiplex assays and ELISA showed that polyI:C significantly increased maternal serum concentrations of interleukin-1β, tumor necrosis factor, and CXCL1 3h after administration. Subsequent experiments tested the role of elevated maternal CXCL1 on behavior of the offspring by administering a CXCR1/CXCR2 antagonist (G31P; 500 μg/kg, i.p.; 1h before, 48 and 96 h after polyI:C treatment). The male offspring of dams treated with polyI:C demonstrated subtle impairments in prepulse inhibition (PPI), impaired associative and crossmodal recognition memory, and altered behavioral flexibility in an operant test battery. While G31P did not completely reverse the behavioral impairments caused by polyI:C, it enhanced PPI during adolescence and strategy set-shifting and reversal learning during young adulthood. These results suggest that while polyI:C treatment significantly increases maternal CXCL1, elevations of this chemokine are not solely responsible for the effects of polyI:C on the behavior of the offspring.

Topics: Animals; Behavior, Animal; Chemokine CXCL1; Chemokine CXCL2; Conditioning, Operant; Cues; Female; Interleukin-8; Male; Mental Disorders; Peptide Fragments; Poly I-C; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Prepulse Inhibition; Rats; Rats, Long-Evans; Receptors, CXCR; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Recognition, Psychology; Schizophrenia

Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway.. We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry.. We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA.. The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age.. We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia.

Topics: Adult; Astrocytes; Cells, Cultured; Cerebral Cortex; Chronic Disease; Female; Humans; Interleukin-6; Interleukin-8; Kynurenic Acid; Kynurenine; Male; Middle Aged; Schizophrenia; Tryptophan; Young Adult

Immune deregulation has been postulated to be one of the mechanisms underlying the pathogenesis of tardive dyskinesia (TD). We hypothesized that interleukins would have a link with TD in schizophrenia patients. In this study, the serum IL-2, IL-6 and IL-8 levels were examined by enzyme-linked immunosorbent assay (ELISA) in schizophrenia patients with TD (n=48) and without TD (n=45), and healthy controls (n=44). The psychopathological symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS). The severity of TD was evaluated using Abnormal Involuntary Movement Scale (AIMS). The results showed that serum IL-2, IL-6 and IL-8 levels were significantly different among schizophrenia patients with TD and without TD and normal controls. Moreover, IL-2 level was significantly correlated with PANSS positive subscale and general subscale in patients with TD and without TD. In addition, IL-2 level was positively correlated with AIMS score in TD patients. The results supported that immune disturbance is related to the schizophrenia patients, especially to the patients with TD and ILs might play an important role in the pathophysiology of schizophrenia patients with TD.

Topics: Adult; Aged; Blood Chemical Analysis; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Movement Disorders; Psychiatric Status Rating Scales; Regression Analysis; Schizophrenia; Severity of Illness Index

Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls.. We recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma Questionnaire (CTQ). Using enzyme-linked immunosorbent assay (ELISA) techniques, we measured peripheral levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α. These immune parameters were compared in schizophrenia with childhood trauma, schizophrenia without childhood trauma and healthy controls.. Patients with childhood trauma had higher levels of IL-6 and TNF-α than patients without trauma and healthy controls, and TNF-α levels correlated with the extent of the trauma. Patients with no trauma had similar immune profiles to controls.. Childhood trauma drives changes, possibly epigenetic, that generate a pro-inflammatory phenotype.

Topics: Adult; Case-Control Studies; Child; Child Abuse; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Parental Death; Phenotype; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Stress, Psychological; Tumor Necrosis Factor-alpha

Inflammatory immune processes have been clearly implicated in the etiopathology of schizophrenia. There are, however, only limited data dealing with immune parameters in the first episode patients with schizophrenia and the course of these parameters during treatment.. The presented study compared plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-alpha in 25 patients with the first episode of schizophrenia with the minimal exposition of antipsychotics before and after treatment and with age and sex matched group of healthy volunteers. Changes in plasma cytokine levels were investigated after 4 weeks of treatment in relationship with the therapeutic outcome.. Our results show significantly increased plasma levels of IL-6 (p≤0.001) and TNF-alpha (p≤0.001) in patients at the admission in comparison with healthy volunteers. After 4 weeks of the treatment the PANSS score decreased (p≤0.001), concurrently the plasma level of IL-6 decreased and TNF-alpha did not show any decrease after treatment. The patients' posttreatment and healthy control group comparison showed higher plasma levels of TNF-alpha (p=0.008) and marginally elevated plasma level of IL-6 (p=0.046) in the posttreatment group. Plasma levels of IL-8 and IL-10 did not show any significant differences.. Our study validated the presence of the proinflammatory state in the first episode of schizophrenia. IL-6 may be considered as a state marker for acute exacerbations and TNF-alpha may be a trait marker of schizophrenia.

Topics: Adult; Antipsychotic Agents; Biomarkers; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Psychiatric Status Rating Scales; Reference Values; Schizophrenia; Schizophrenic Psychology; Tumor Necrosis Factor-alpha

Maternal infection during pregnancy has been repeatedly associated with increased risk for schizophrenia. Nevertheless, most viruses do not cross the placenta; therefore, the damaging effects to the fetus appear to be related to maternal antiviral responses to infection (e.g. proinflammatory cytokines). Fetal exposure to the proinflammatory cytokine interleukin-8 (IL-8) has been significantly associated with risk of schizophrenia in offspring. This study sought to determine the association between fetal exposure to IL-8 and structural brain changes among schizophrenia cases and controls.. Subjects were 17 cases diagnosed with schizophrenia from the Developmental Insult and Brain Anomaly in Schizophrenia (DIBS) study. Psychiatric diagnoses were determined among offspring with semi-structured interviews and medical records review. IL-8 was determined from assays in archived prenatal sera and volumetric analyses of neuroanatomical regions were obtained from T1-weighted magnetic resonance imaging in adulthood. Eight controls were included for exploratory purposes.. Among cases, fetal exposure to increases in IL-8 was associated with significant increases in ventricular cerebrospinal fluid, significant decreases in left entorhinal cortex volumes and significant decreases in right posterior cingulate volumes. Decreases that approached significance also were found in volumes of the right caudate, the putamen (bilaterally), and the right superior temporal gyrus. No significant associations were observed among controls.. Fetal exposure to elevations in maternal IL-8 led to structural neuroanatomic alterations among cases in regions of the brain consistently implicated in schizophrenia research. In utero exposure to elevations in IL-8 may partially account for brain disturbances commonly found in schizophrenia.

Topics: Adult; Brain; Cohort Studies; Cytokines; Female; Humans; Image Processing, Computer-Assisted; Interleukin-8; Magnetic Resonance Imaging; Male; Pregnancy; Prenatal Diagnosis; Prenatal Exposure Delayed Effects; 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.

Topics: Acute Disease; Adult; Control Groups; Cytokines; Diagnostic and Statistical Manual of Mental Disorders; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-4; Interleukin-8; Male; Middle Aged; Psychiatric Status Rating Scales; Receptors, Interleukin-2; Schizophrenia; Schizophrenic Psychology; Tumor Necrosis Factor-alpha

Accumulating evidence suggests that prenatal exposure to infection contributes to the etiology of schizophrenia. This line of investigation has been advanced by birth cohort studies that utilize prospectively acquired data from serologic assays for infectious and immune biomarkers. These investigations have provided further support for this hypothesis and permitted the investigation of new infectious pathogens in relation to schizophrenia risk. Prenatal infections that have been associated with schizophrenia include rubella, influenza, and toxoplasmosis. Maternal cytokines, including interleukin-8, are also significantly increased in pregnancies giving rise to schizophrenia cases. Although replication of these findings is required, this body of work may ultimately have important implications for the prevention of schizophrenia, the elaboration of pathogenic mechanisms in this disorder, and investigations of gene-environment interactions.

Topics: Animals; Biomarkers; Communicable Diseases; Female; Herpesvirus 2, Human; Humans; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Schizophrenia; Time Factors; Toxoplasma; Tumor Necrosis Factor-alpha

Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection and in other inflammatory processes. The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 (IL-8), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects.. The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort, born 1959-1967. Cases (N=59) were subjects diagnosed with schizophrenia spectrum disorders (mostly schizophrenia and schizoaffective disorder) who had available second-trimester maternal serum samples. Comparison subjects (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder, and were matched to subjects with schizophrenia for date of birth, gender, length of time in the cohort, and availability of maternal sera. Maternal second-trimester serum levels of IL-8, IL-1beta, IL-6, and TNF-alpha were determined by sandwich enzyme-linked immunosorbent assay.. The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects. There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta, IL-6, or TNF-alpha.. Using prospectively collected prenatal sera in a large and well-characterized birth cohort, the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring. These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia. Moreover, these results may have important implications for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder.

Topics: Adult; Case-Control Studies; Cohort Studies; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Second; Prenatal Exposure Delayed Effects; Risk Factors; Schizophrenia; Tumor Necrosis Factor-alpha

Cytokines have been one of the recent focal points of immunological research in schizophrenia. The present study was to assess the serum levels of some of interleukins in schizophrenia and their relationships with the psychopathological parameters. Seventy physically healthy Chinese patients, who met DSM-III-R criteria for schizophrenia and who were drug-free for at least 2 weeks, were compared with 30 age- and sex-matched Chinese normal controls. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Serum levels of IL-6 and IL-8 were measured by sandwich enzyme-linked immunosorbent assay (ELISA), and serum IL-2 level was assayed by radioimmunometric assay (RIA). Serum levels of IL-2, IL-6 and IL-8 were significantly elevated in patients with a chronic form of schizophrenia (all p<0.05). There was a significant inverse relationship between IL-2 level and the PANSS positive subscale P (r=-0.31, p=0.006) and a significant positive correlation between IL-8 level and PANSS negative subscale N (r=0.25, p=0.036) in schizophrenic patients. In control subjects, a significant and positive relationship between serum IL-2 and IL-6 (r=0.513, p=0.004) was noted, whereas, there was a significant and negative relationship between IL-2 and IL-8 in schizophrenic patients (r=-0.28, p=0.02). Our data confirms and supports the view that immune disturbance is involved in schizophrenia, which is compatible with the possibility that Chinese schizophrenic patients have an ongoing autoimmune process. This immune disturbance is related to the subgroup of schizophrenic patients with characteristic clinical variables. The dysfunction of interaction or inter-adjustment between different cytokines may exist in schizophrenic patients.

Topics: Adult; Analysis of Variance; Case-Control Studies; China; Female; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Statistics, Nonparametric

There is now evidence that schizophrenia may be accompanied by an activation of the monocytic and T-helper-2 (Th-2) arms of cell-mediated immunity (CMI) and by various alterations in the Th-1 arm of CMI. There is also evidence that repeated administration of typical and atypical antipsychotics may result in negative immunomodulatory effects. This study was carried out to examine (1) the serum concentrations of interleukin-8 (IL-8), IL-10, the soluble CD8 (sCD8) and the leukemia inhibitory factor receptor (LIF-R) in nonresponders to treatment with typical neuroleptics as compared with normal volunteers and responders to treatment; and (2) the effects of atypical antipsychotics on the above immune variables. The latter were determined in 17 nonresponders to treatment with neuroleptics and in seven normal volunteers and 14 schizophrenic patients who had a good response to treatment with antipsychotic agents. The nonresponders had repeated measurements of the immune variables before, and 2 and 4 months after treatment with clozapine or risperidone. Serum IL-8 and IL-10 were significantly higher in schizophrenic patients than in normal controls. The serum concentrations of the sCD8 were significantly increased 2 months, but not 4 months, after starting treatment with atypical antipsychotics. Serum LIF-R concentrations were significantly increased 2 and 4 months after starting treatment with atypical antipsychotics. It is concluded that: (1) schizophrenia is characterized by an activation of both pro-inflammatory and anti-inflammatory aspects of cell-mediated immunity; (2) prolonged treatment with atypical antipsychotics may increase the anti-inflammatory capacity of the serum in schizophrenic patients by increasing serum LIF-R concentrations; and (3) short-term treatment with clozapine may induce signs of immune activation which disappear upon prolonged treatment.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Case-Control Studies; Clozapine; Drug Resistance; Female; Humans; Interleukin-10; Interleukin-8; Leukemia Inhibitory Factor Receptor alpha Subunit; Male; Middle Aged; Receptors, Cytokine; Receptors, OSM-LIF; Regression Analysis; Schizophrenia

Schizophrenic patients are reported to have immunological dysfunction, however, the immune response to surgery in schizophrenic patients remains unclear. We measured plasma interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) before, during and after colectomy, hemicolectomy and sigmoidectomy in 25 chronic schizophrenic patients (Group S) and 25 control patients (Group C) using ELISA assays. We could find no significant difference in the baseline plasma concentrations of IL-6, IL-8 and TNF-alpha between Group S and Group C. Plasma IL-6 concentrations (32.1 (30.3) and 15.8 (9.6) pg/ml) in Group S at the end of the operation and 24 h after surgery were significantly lower than 76.9 (37.1) and 35.1 (21.5) pg/ml of Group C. Plasma IL-8 concentration (6.1 (2.8)) in Group S at the end of the operation was significantly lower than 8.7 (4.2) pg/ml of Group C. There were no significant changes in plasma TNF-alpha concentration throughout the study period in either group. Plasma cortisol concentrations of schizophrenic patients during surgery were significantly lower than those of control patients. The plasma IL-6 concentrations correlated with plasma cortisol concentrations in either group. We conclude that proinflammatory cytokine response to abdominal surgery is inhibited in schizophrenic patients.

Topics: Adult; Aged; C-Reactive Protein; Case-Control Studies; Female; Humans; Hydrocortisone; Interleukin-6; Interleukin-8; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology; Stress Disorders, Post-Traumatic; Stress, Physiological; Surgical Procedures, Operative; Tumor Necrosis Factor-alpha

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Case-Control Studies; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Receptors, Interleukin-2; Risperidone; Schizophrenia; Tumor Necrosis Factor-alpha