Elevated macrophage migration inhibitory factor and decreased transforming growth factor-beta levels in major depression--no influence of celecoxib treatment.

OBJECTIVES: The involvement of an immune process in the pathophysiology of major depression disorder (MDD) was substantiated by studies demonstrating elevated levels of proinflammatory cytokines and prostaglandin E(2) (PGE(2)). Cyclooxygenase-2 (COX-2) inhibitors lead to a reduced production of PGE(2) and have been shown to improve depressive symptoms. We investigated the three immune parameters macrophage migration inhibitory factor (MIF), transforming growth factor-ß (TGF-ß) and soluble CD14 (sCD14) in a randomized, placebo-controlled trial of the COX-2 inhibitor celecoxib as add-on therapy in patients with MDD treated with reboxetine. METHODS: Thirty-two patients with depression and 20 healthy controls participated in the study. The patients were treated with reboxetine and celecoxib or placebo. Immune parameters were measured from serum at baseline, after three and five weeks using ELISA. RESULTS: Celecoxib as add-on strategy resulted in a significant reduction of Hamilton Depression Scale scores compared to placebo. Depressed patients showed significantly elevated MIF (p < 0.001) and reduced TGF-ß (p = 0.006) concentrations at baseline. There was no difference in sCD14-concentrations. There was no difference between the placebo and the celecoxib group and no change over time. LIMITATIONS: Limitations of the study are the relatively small sample size and lack of functional assessment of HPA axis in parallel. CONCLUSIONS: MIF is a promising new candidate in the neuro-immune interplay that may link depressive symptoms, altered immune state and HPA-axis dysregulation. Reduced levels of TGF-ß replicate previous findings and support the importance of this regulatory cytokine in major depressive disorder.

Reversal of imbalance between kynurenic acid and 3-hydroxykynurenine by antipsychotics in medication-naïve and medication-free schizophrenic patients.

The association between the pro-inflammatory state of schizophrenia and increased tryptophan degradation into kynurenine has been reported. However, the relationship between metabolites from subdivisions of the kynurenine pathway, kynurenic acid and 3-hydroxykynurenine, remains unknown. The present study tested the relationship between these kynurenine metabolites in the plasma of medication-naïve (n=35) or medication-free (n=18) patients with schizophrenia at admission and following 6-week antipsychotic treatment compared to healthy controls (n=48). The plasma concentrations of kynurenic acid (nmol/l) were lower (difference=-8.44 (-13.22 to -3.65); p=0.001) and of 3-hydroxykynurenine (nmol/l) were higher (difference=11.24 (8.11-14.37); p<0.001) in the patients compared with the healthy controls. The kynurenic acid/kynurenine (difference=-2.75 (-5.115 to -0.336); p=0.026) and kynurenic acid/3-hydroxykynurenine (difference=-1.08 (-1.431 to -0.729); p<0.001) ratios were also lower in the patients. After the 6-week treatment, the patients' plasma kynurenic acid levels (difference=3.85 (-0.23 to 7.94); p=0.064) showed a trend towards an increase, whereas plasma 3-hydroxykynurenine levels (difference=22.41 (19.76-25.07); p<0.001) decreased. As a consequence, the kynurenic acid/3-hydroxykynurenine ratio (difference=-4.41 (-5.51 to -3.3); p<0.001) increased. Higher initial plasma kynurenic acid levels on admission or increased kynurenic acid/kynurenine ratio after treatment were associated with reduction of clinical symptoms scores upon discharge although higher kynurenic acid/kynurenine on admission may induce higher positive symptoms score. In contrast, higher 3-hydroxykynurenine is associated with lower positive symptoms score. These results indicate that there is an imbalance in the kynurenine pathway in schizophrenia. The 6-week antipsychotic treatment may partially reverse the imbalance in kynurenine metabolism and that in turn induces clinical response.

A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis.

Screening newborns for cystic fibrosis (CF) is considered to be an ethical undertaking in regions with a significant incidence of the condition. Current screening protocols result in recognition of infants with an equivocal diagnosis. A survey of European practice suggested inconsistencies in the evaluation and management of these infants. We have undertaken a consensus process using a modified Delphi method. This has enabled input of CF specialists from a wide geographical area to a rigorous process that has provided a clear pathway to a consensus statement. A core group produced 21 statements, which were modified over a series of three rounds (including a meeting arranged at the European CF Conference). A final document of 19 statements was produced, all of which achieved a satisfactory level of consensus. The statements cover four themes; sweat testing, further assessments and investigations, review arrangements and database. This consensus document will provide guidance to CF specialists with established screening programmes and those who are in the process of implementing newborn screening in their region.

Effects of experimentally induced panic attacks on neuroimmunological markers.

Since little is known concerning regulation of immunological parameters in rapid changing psychiatric states like panic attacks, we measured cytokines at different time points in healthy subjects, which underwent experimental panic induction using the CCK-4 paradigm. Apart from a challenge related IL-6 increase, we could not observe any changes of neuroimmunological markers in relation to acute anxiety with regard to time and group. Herein we conducted for the first time a new approach to immunological research in panic disorder, suggesting immune changes are more related to long term disease stress.

Some cases of common variable immunodeficiency may be due to a mutation in the SBDS gene of Shwachman-Diamond syndrome.

Known genetic defects currently account for only a small proportion of patients meeting criteria for 'probable' or 'possible' common variable immunodeficiency (CVID). A 59-year-old male with a 12-year history of CVID on intravenous immunoglobulin (IVIG) is presented who developed bronchiectasis, cytopenias and malabsorption that are recognized complications of CVID. Work-up for his malabsorption suggested the possibility of Shwachman-Diamond syndrome, confirmed by mutation testing. With the identification of the molecular defect in Shwachman-Diamond syndrome (SDS), it is becoming clear that not all SDS patients have the prominent features of neutropenia or pancreatic malabsorption. A meta-analysis of published immunological defects in SDS suggests that four of 14 hypogammaglobulinaemic SDS patients meet criteria for 'possible' CVID. Mutations in the SBDS gene may therefore be the fifth identified molecular defect in CVID.

The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view.

This overview presents a hypothesis to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. In schizophrenia, a glutamatergic hypofunction is discussed to be crucially involved in dopaminergic dysfunction. This view is supported by findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction is mediated by NMDA (N-methyl-D-aspartate) receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYN-A). KYN-A also blocks the nicotinergic acetycholine receptor, i.e. increased KYN-A levels can explain psychotic symptoms and cognitive deterioration. KYN-A levels are described to be higher in the CSF and in critical CNS regions of schizophrenics. Another line of evidence suggests that of the immune system in schizophrenic patients is characterized by an imbalance between the type-1 and the type-2 immune responses with a partial inhibition of the type-1 response, while the type-2 response is relatively over-activated. This immune constellation is associated with the inhibition of the enzyme indoleamine 2,3-dioxygenase (IDO), because type-2 cytokines are potent inhibitors of IDO. Due to the inhibition of IDO, tryptophan is predominantly metabolized by tryptophan 2,3-dioxygenase (TDO), which is located in astrocytes, but not in microglia cells. As indicated by increased levels of S100B, astrocytes are activated in schizophrenia. On the other hand, the kynurenine metabolism in astrocytes is restricted to the dead-end arm of KYN-A production. Accordingly, an increased TDO activity and an accumulation of KYN-A in the CNS of schizophrenics have been described. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g. the use of antiinflammatory cyclooxygenase-2 inhibitors, which also are able to directly decrease KYN-A, are discussed.

[Immunological aspects of depressive disorders]. / Immunologische Aspekte bei depressiven Störungen.

Beside the monoaminergic deficiency concept as a pathophysiological correlate of depressive disorder, the role of increased glutamatergic neurotransmission is increasingly being discussed. Causes and interactions of these neurotransmitter disturbances are not fully understood to date. This review presents a concept integrating actual findings of the neurotransmitter dysregulations with immunological and morphological findings in depressive disorder. Several intertwined mechanisms seem to be important: The common cause of serotonin deficiency and increased glutamatergic neurotransmission seems to be the increase of proinflammatory cytokines. Immune activation with increased production of proinflammatory cytokines activate the tryptophan- and serotonin-degradating enzyme indolamine-2,3-dioxygenase (IDO). The increased consumption of serotonin and its precursor tryptophan due to IDO activation may explain the reduced availability of serotonin in depression. In inflammatory somatic disorders, depressive mood is associated with an increase of proinflammatory cytokines and increased consumption of tryptophan. This activation of IDO by proinflammatory cytokines leads to the production of glutamatergic agonists. In the CNS, IDO is activated during inflammatory processes primarily in microglial cells. Therefore the astrocyte:microglial balance in depression is important. The observed decrease of astrocytes in the CNS of depressive patients may contribute to a regulatory fault in the activity of IDO in microglial cells but also can cause an alteration of the glutamatergic neurotransmission. By this mechanism, the dysbalance of the immune response and the astrocyte:microglia dysbalance may contribute to serotonergic deficiency and glutamatergic overproduction in depression. The further search for new antidepressant therapeutic mechanisms should take into regard anti-inflammatory substances, e.g. cyclo-oxygenase-2 (COX-2)-inhibitors.

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression.

Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-gamma, or tumor necrosis factor-alpha activate the tryptophan- and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes - counteracting this metabolism due to the lack of an enzyme of this metabolism - have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid.

Association of cognitive deficits with elevated homocysteine levels in euthymic bipolar patients and its impact on psychosocial functioning: preliminary results.

OBJECTIVES: Elevated homocysteine (Hcy) levels have been demonstrated to have a negative impact on cognitive functioning in healthy elderly people. Further studies suggest that they are an independent risk factor for dementia, in particular for Alzheimer's disease. Bipolar disorder is also associated with cognitive impairment. However, the pathophysiological mechanisms of these deficits have not been elucidated yet. This study examines the role of Hcy on cognition and its impact on psychosocial functioning in euthymic bipolar patients. METHODS: A total of 55 euthymic bipolar patients and 17 healthy controls were enrolled in the study. Neuropsychological assessments consisted of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Trail Making Test (TMT), the Weschler Adult Intelligence Scale, 3(rd) edition (WAIS-III) subtest Letter-Number Sequencing Test (LNST) and the HAWIE-R (German version of the WAIS-R) subtest Information. Psychosocial functioning was assessed using the Social Adjustment Scale (SAS). To obtain plasma levels of Hcy, blood samples were collected in EDTA tubes, immediately put on ice, centrifuged within 15 min and stored at -80 degrees C. Total Hcy concentration was measured using high-performance liquid chromatography. RESULTS: In the neuropsychological tests, patients differed significantly from healthy controls on the TMT B and the RBANS composite indices Language, Attention and Total Score. No differences were found on the HAWIE-R subtest Information, the TMT A, LNST or the RBANS composite indices Immediate Memory, Visuospatial/Constructional Abilities and Delayed Memory. Mean Hcy levels were 9.8 +/- 3.2 microm/L in the patient group and 7.8 +/- 2.1 microm/L in the control group, respectively (p = 0.012). In the patient group Hcy levels significantly correlated with gender, diagnosis and RBANS index scores for Immediate Memory, Language, Attention and Total Score. Linear regression analyses revealed a significant and independent association of Hcy levels with Immediate Memory and TMT B scores in the patient group. Homocysteine levels did not correlate with any measure in the control group. Spearman's correlations indicated that psychosocial functioning in bipolar patients is not associated with clinical variables apart from time in remission. However, it correlated significantly with working memory measures (LNST). No relationship could be determined between psychosocial functioning and Hcy plasma levels. CONCLUSIONS: Elevated Hcy levels seem to be associated with cognitive impairment in euthymic bipolar patients, but not with psychosocial functioning. More studies are needed to clarify the role of Hcy in cognition in bipolar disorder.

[Immunology in schizophrenic disorders]. / Immunologische Aspekte bei schizophrenen Störungen.

This manuscript deals with whether immune-mediated mechanisms of inflammation contribute to the pathogenesis of schizophrenia. A model is presented which integrates psychoneuroimmunologic findings and actual results from pharmacological, neurochemical, and genetic studies in schizophrenia. A pivotal role in the neurobiology of schizophrenia is played by dopaminergic neurotransmission, which is modulated by influences of the glutamatergic system. The decreased function of the glutamate system described in schizophrenia seems primarily mediated by N-methyl-D-aspartate (NMDA) receptor antagonism. Kynurenine acid is the only known endogenous NMDA receptor antagonist. In higher concentrations it blocks the NMDA receptor, but in lower concentrations it blocks the nicotinergic acetylcholin receptor, which has a prominent role in cognitive functions. Therefore, higher levels of kynurenine acid may explain psychotic symptoms and cognitive dysfunction. Several findings point out that prenatal infection, associated with an early sensitisation of the immune system, may result in an imbalance of the immune response (type 1 vs type 2) in schizophrenia. This immune constellation leads to inhibition of the enzyme indoleamin dioxigenase (IDO). It and tryptophane 2,3-dioxygenase (TDO) both catalyse the degradation from tryptophan to kynurenine. Due to the inhibition of IDO, tryptophan is metabolised to kynurenine primarily by TDO. In the CNS, TDO is located only in astrocytes, which are in particular activated in schizophrenia and in which kynurenine acid is the final product and can not be further metabolised. Therefore kynurenine acid accumulates in the CNS of schizophrenics and - due to its NMDA-antagonistic properties - leads to cognitive dysfunction and psychotic symptoms. This model describes the pathway of immune-mediated glutamatergic-dopaminergic dysregulation, which may lead to the clinical symptoms of schizophrenia. Therapeutic consequences (e.g. cyclo-oxygenase-2 inhibitors) are discussed.

The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine.

Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E(2) (PGE(2)), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE(2) production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4-10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.

Risperidone plasma levels, clinical response and side-effects.

INTRODUCTION: Assessment of the relation between oral risperidone dose, serum drug levels and clinical response may provide important information for rational treatment decisions. Inter-individual differences in the liver cytochrome P450 system, especially in the CYP2D6 subsystem, which account for a significant portion of risperidone metabolism, may also influence plasma drug levels and alter clinical response parameters. We thus prospectively investigated risperidone serum concentrations in relation to clinical efficacy and side-effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters. METHODS: Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6-week open dose clinical trial. Weekly assessments including CGI and PANSS ratings to assess psychopathology; SAS to assess medication side effects; and blood draws to quantify steady state plasma levels of risperidone and 9-OH-risperidone were carried out. In addition, major CYP2D6 polymorphisms including alleles *4, *6 and *14 were genotyped. RESULTS: Eighty-two patients were recruited. Mean oral dose of risperidone was 4.3 +/- 0.9 mg. Mean plasma level of both risperidone and 9-OH-risperidone together ("active moiety") was 41.6 +/- 26.6 ng/ml. Significant improvements in PANSS scales and the various subscales ensued. There was a positive linear correlation between active moiety plasma levels and dose (r = 0.291, p = 0.015) and between risperidone and 9-OH-risperidone levels (r = 0.262; p = 0.016). Nonresponders to pharmacotherapy (PANSS-Improvement < 30%) showed significantly higher active moiety plasma levels (49.9 +/- 30.7 ng/ml) than responders (38.2 +/- 17.0 ng/ml; p = 0.045) without significantly higher oral doses (p = 0.601). Patients with longer illness duration (> or = 3 years) had significantly higher plasma drug levels than those with a shorter course (< 3 years; p = 0.039). Extrapyramidal side effects (EPS) and plasma levels were not correlated (r = 0.028; p = 0.843), but higher plasma levels at week 2 predicted an incidence for EPS (p < 0.050). Accordingly, patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course. Eight patients (9.8%) were heterozygous carriers of the CYP2D6 allele *4. CYP2D6 polymorphisms did not predict clinical response, but predicted a tendential increase in the plasma risperidone to 9-OH-risperidone ratio (0.5 +/- 0.6 vs. 1.9 +/- 1.8; p = 0.120). DISCUSSION: The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9-OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses. The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy, but affected risperidone to 9-OH-risperidone ratios. Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects. Conversely, the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances. Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration. The high inter-individual variability in risperidone and 9-OH-risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinically relevant active moiety.

Psychotropic effects of COX-2 inhibitors--a possible new approach for the treatment of psychiatric disorders.

Cyclooxygenase-2 (COX-2)--constitutively expressed in the CNS--is suggested to have an important functional role in the CNS. COX-2 interacts with neurotransmitters such as acetylcholine, serotonin, and glutamate, but is also involved in the regulation of immune system and in inflammation in the central nervous system (CNS) via effects of prostaglandins, in particular prostaglandin E (2). Recently, a role for the new generation of selective COX-2 inhibitors in the treatment of psychiatric disorders is discussed. Until now, COX-2 inhibitors have failed to show therapeutic effects in Alzheimer's disease, but studies from basic research point to a possible effect on cognition. A clinical effect of the COX-2 inhibitor celecoxib on cognition was observed in schizophrenic patients. The therapeutic effect of celecoxib add-on treatment to the atypical antipsychotic risperidone, however, is not restricted to cognition. A general effect on symptoms of schizophrenia was observed, which supports the view that an immunological/inflammatory process is involved in the pathogenesis of schizophrenia. In depression, however, signs of inflammation have been described since many years. Although results of clinical studies with COX-2 inhibitors in depression are still lacking, clinical improvement of a depressive syndrome has been observed in patients, who have been treated with rofecoxib due to other indications. These preliminary clinical data are encouraging for therapeutic effects of the selective COX-2 inhibitors in psychiatric disorders, although these effects have to be confirmed in bigger clinical studies.

Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism.

Dopamine deficiency is characteristic of Parkinson's disease (PD) and treatments aim at elevating levels by administration of its precursor L-dihydroxyphenylalanine (L-DOPA), or inhibiting monoamine oxidases (MAOs), thus preventing its breakdown. Reports of improvements in PD patients treated with Banisteriopsis caapi extracts stimulated investigation of B. caapi stem extract and its two ingredients, harmine and harmaline for these activities. Tests for MAO inhibition using liver homogenate showed that extract and harmaline showed a concentration-dependent inhibition of MAO A (IC(50) 1.24 microg/ml and IC(50) 4.54 nM, respectively) but had little effect on MAO B activity. The extract at 2.5 mg/ml caused a highly significant increase in release of [3H]dopamine from rat striatal slices, as did 200 microM harmine and 6 microM harmaline. In both these experiments, the amount of harmine present could not account for the total activity of the extract. The ability of harmine and harmaline to stimulate dopamine release is a novel finding. These results give some basis to the reputed usefulness of B. caapi stem extract in the treatment of PD.

Evidence for an altered tryptophan metabolism in fibromyalgia.

Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesized underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia.

No association between anti-myelin oligodendrocyte glycoprotein antibodies and serum/cerebrospinal fluid levels of the soluble interleukin-6 receptor complex in multiple sclerosis.

Myelin-oligodendrocyte glycoprotein (MOG) specific antibodies (abs) are involved in autoantibody-mediated demyelination possibly contributing to lesion development in multiple sclerosis (MS). Interleukin-6 (IL-6) has been reported to play a crucial role for the pathogenesis of a MOG-induced animal model of MS. To investigate the link between anti-MOG abs production and IL-6 up-regulation in MS we determined the presence of anti-MOG abs and measured concentrations of IL-6 and its soluble receptors (sIL-6RC) in paired serum and cerebrospinal fluid (CSF) samples of MS patients and serum samples of age-matched healthy controls (HC). Anti-MOG abs were detected in 75% of MS sera, 57% of MS CSF samples and 20% of HC sera. There was no difference in IL-6 and sIL-6RC levels between anti-MOG abs positive and negative samples. Thus, no association between the presence of anti-MOG abs and serum/CSF levels of IL-6/sIL-6RC was found.