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There is extensive bi-directional communication between the brain and the immune system in both health and disease. In recent years, the role of an altered immune system in the etiology of major psychiatric disorders has become more apparent. Studies have demonstrated that some patients with major psychiatric disorders exhibit characteristic signs of immune dysregulation and that this may be a common pathophysiological mechanism that underlies the development and progression of these disorders. Furthermore, many psychiatric disorders are also often accompanied by chronic medical conditions related to immune dysfunction such as autoimmune diseases, diabetes and atherosclerosis. One of the major psychiatric disorders that has been associated with an altered immune system is schizophrenia, with approximately one third of patients with this disorder showing immunological abnormalities such as an altered cytokine profile in serum and cerebrospinal fluid. An altered cytokine profile is also found in a proportion of patients with major depressive disorder and is thought to be potentially related to the pathophysiology of this disorder. Emerging evidence suggests that altered immune parameters may also be implicated in the neurobiological etiology of autism spectrum disorders. Further support for a role of immune dysregulation in the pathophysiology of these psychiatric disorders comes from studies showing the immunomodulating effects of antipsychotics and antidepressants, and the mood altering effects of anti-inflammatory therapies. This review will not attempt to discuss all of the psychiatric disorders that have been associated with an augmented immune system, but will instead focus on several key disorders where dysregulation of this system has been implicated in their pathophysiology including depression, schizophrenia and autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called 'IFN type I signature', in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF).Methods: Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS.Results: An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren's Syndrome Disease Activity Index scores; higher anti-Ro52, anti-Ro60 and anti-La autoantibodies; higher rheumatoid factor; higher serum IgG; lower C3, lower absolute lymphocyte and neutrophil counts; (b)higher BAFF gene expression in monocytes. In addition, serum of signature-positive patients induced BAFF gene expression in monocytes.Conclusions: The monocyte IFN type I signature identifies a subgroup of patients with pSS with a higher clinical disease activity together with higher BAFF mRNA expression. Such patients might benefit from treatment blocking IFN type I production or activity. [ABSTRACT FROM AUTHOR]

Chronic purulent rhinosinusitis (CPR) is an inflammatory condition of unknown origin. Although various medical and surgical treatment modalities are available, 5-10% of patients remain refractory. Immune deficiency is one of the underlying risk factors for this disease. Earlier studies demonstrated disturbances in cell-mediated immunity and defects in monocyte chemotaxis in CPR. Treatment with the thymic hormone preparation thymostimulin led to significant clinical improvement in patients and in vitro restoration of monocyte chemotaxis. Unfortunately, thymostimulin became unavailable, which has led to recent interest in the immunomodulatory effects of the thymic peptide thymosin α1, which has demonstrated some benefit for CPR. Our current in vitro work focuses on the potential effects of thymosin α1 on monocyte function and gene expression profiles in order to understand its effects and mechanisms of action. Future clinical studies will evaluate the potential significance of thymosin α1 in treatment of CPR patients. [ABSTRACT FROM AUTHOR]

Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell subpopulations via six-color flow cytometry, including CD8+ and CD4+ T cells, CD4+ T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+ T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+ naive, memory, natural CD4+CD25+FoxP3+ Treg, and Th2 T cells, whereas CD8+ T cells were normal. CD4+ and CD8+ T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+ T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+ T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point. [ABSTRACT FROM AUTHOR]

Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell subpopulations via six-color flow cytometry, including CD8+ and CD4+ T cells, CD4+ T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+ T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+ naive, memory, natural CD4+CD25+FoxP3+ Treg, and Th2 T cells, whereas CD8+ T cells were normal. CD4+ and CD8+ T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+-T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+ T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point. [ABSTRACT FROM AUTHOR]

The non-obese diabetic (NOD) mouse is a widely used animal model for the study of human diabetes. Before the start of lymphocytic insulitis, DC accumulation around islets of Langerhans is a hallmark for autoimmune diabetes development in this model. Previous experiments indicated that an inflammatory influx of these DCs in the pancreas is less plausible. Here, we investigated whether the pancreas contains DC precursors and whether these precursors contribute to DC accumulation in the NOD pancreas. Fetal pancreases of NOD and control mice were isolated followed by FACS using ER-MP58, Ly6G, CD11b and Ly6C. Sorted fetal pancreatic ER-MP58+ cells were cultured with GM-CSF and tested for DC markers and antigen processing. CFSE labeling and Ki-67 staining were used to determine cell proliferation in cultures and tissues. Ly6Chi and Ly6Clow precursors were present in fetal pancreases of NOD and control mice. These precursors developed into CD11c+MHCII+CD86+ DCs capable of processing DQ-OVA. ER-MP58+ cells in the embryonic and pre-diabetic NOD pancreas had a higher proliferation capacity. Our observations support a novel concept that pre-diabetic DC accumulation in the NOD pancreas is due to aberrant enhanced proliferation of local precursors, rather than to aberrant 'inflammatory infiltration' from the circulation. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Biologicals and small inhibitory molecules are used to treat inflammatory diseases, but their efficacy varies upon clinical application. Using a whole orbital tissue culture system, we tested the potential efficacy of imatinib mesylate (a tyrosine kinase inhibitor that blocks platelet-derived growth factor (PDGF)-receptor, c-Abl and c-Kit activity) and adalimumab (an anti-TNF-α antibody) for the treatment of Graves' ophthalmopathy (GO). METHODS: Orbital fat tissue from GO patients (n=10) was cultured with or without imatinib mesylate or adalimumab. PDGF-B and tumour necrosis factor (TNF)-α mRNA expression levels were determined in the primary orbital tissue, and interleukin (IL)-6 and hyaluronan were measured in tissue-culture supernatants. RESULTS: Imatinib mesylate significantly (p=0.005) reduced IL-6 and hyaluronan production. The inhibition of hyaluronan production correlated positively and significantly (p<0.05) with the PDGF-B mRNA level in the primary tissue. Adalimumab also significantly (p=0.005) reduced IL-6 production. The amount of IL-6 inhibition correlated positively with the TNF-α mRNA level in the primary tissue, but this was not significant. CONCLUSIONS: Imatinib mesylate can be expected to reduce inflammation and tissue remodelling in GO, while adalimumab can be mainly expected to reduce inflammation. This in vitro tissue-culture model may, in future, prove valuable to test novel therapeutics for their presumed effect in GO as well as in other inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Postpartum psychosis is a life-threatening psychiatric emergency, which often occurs without significant premorbid symptoms. Although many studies have postulated an involvement of the immune and endocrine systems in the onset of postpartum psychosis, the specific aetiological factors have remained unknown.Aims: To examine the hypothesis that autoimmune thyroid dysfunction may be associated with the onset of postpartum psychosis.Method: Thirty-one consecutive primiparous women with no prior psychiatric history were referred to our in-patient unit for postpartum psychosis. The control group (n = 117) comprised primiparous women with consecutive deliveries at a community practice. Blood samples were obtained from all participants at 4 weeks and 9 months postpartum. Thyroperoxidase antibody levels were quantified as immunological measures of autoimmune thyroid disease (AITD). Thyroid-stimulating hormone and free thyroxine levels were measured to assess clinical thyroid dysfunction.Results: At 4 weeks postpartum and prior to the initiation of mood stabiliser therapy, 19% of women with postpartum psychosis had AITD compared with only 5% in the control group. Women with both postpartum psychosis and AITD had a dramatically higher risk of progression to clinical thyroid dysfunction (67%) than control participants with AITD (20%).Conclusions: Women with postpartum psychosis are at higher risk not only of AITD but also of clinical thyroid failure. These data implicate thyroid function as an important clinical outcome in patients with postpartum psychosis. Further, AITD represents a potentially strong aetiological factor for the development of postpartum psychosis. Therefore, screening for thyroperoxidase antibodies is warranted in patients with postpartum psychosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Monocytes in childhood-onset type 1 diabetes show distinct gene expression. We hypothesize that monocyte activation in monozygotic (MZ) twin pairs discordant for childhood-onset type 1 diabetes could reflect distinct stages of the disease process including diabetes susceptibility (differences between twins, both diabetic and nondiabetic, and control subjects) and/or disease progression (differences between diabetic and nondiabetic twins). RESEARCH DESIGN AND METHODS--We studied patterns of inflammatory gene expression in peripheral blood monocytes of MZ twin pairs (n = 10 pairs) discordant for childhood-onset type 1 diabetes, normal control twin pairs (n = 10 pairs), and healthy control subjects (n = 51) using quantitative-PCR (QPCR). We tested the 24 genes previously observed by whole genome analyses and verified by Q-PCR in autoimmune diabetes and performed a hierarchical cluster analysis. RESULTS--Of 24 genes abnormally expressed in childhood-onset type 1 diabetes, we revalidated abnormal expression in 16 of them in diabetic twins including distinct sets of downregulated (P < 0.03) and upregulated (P < 0.02) genes. Of these 16 genes, 13 were abnormally expressed in nondiabetic twins, implicating these genes in diabetes susceptibility (P < 0.044 for all). Cluster analysis of monocyte gene-expression in nondiabetic twins identified two distinct, mutually exclusive clusters, while diabetic twins had a network of positively correlated genes. CONCLUSIONS--Patients with childhood-onset type 1 diabetes show abnormal monocyte gene--expression levels with an altered gene-expression network due to gene-environment interaction. Importantly, perturbed gene-expression clusters were also detected in nondiabetic twins, implicating monocyte abnormalities in susceptibility to diabetes. Diabetes 59:1751-1755, 2010 [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effect of genetic and environmental influences on pro-inflammatory monocytes in bipolar disorder (BD). It mentions the concept of bipolar disorder, the necessary laboratory methods to be used, and the statistical analysis on the study. Result show that the occurrence of the connection between the monocyte pro-inflammatory gene-expression and BD found was due to common environmental factors.

OBJECTIVE--There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes. RESEARCH DESIGN AND METHODS--We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) (n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported. RESULTS--We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients. CONCLUSIONS--Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories. Diabetes 57:2768-2773, 2008 [ABSTRACT FROM AUTHOR]

The article presents a research on mood disturbances associated with an activated inflammatory response system in patients with bipolar disorders. It aims to determine the expression pattern of proinflammatory genes in monocytes on bipolar patients. The research was conducted in an academic research setting in Netherlands, where 42 bipolar patients, 54 offspring of bipolar parent, and 70 healthy participants were subjected with quantitative polymerase chain reaction, or Q-PCR. Results proved that many of bipolar patients, and offspring of bipolar parents have an inflammatory gene expression signature.

Objectives: To study the ex vivo interleukin (IL)-1 β and IL-6 production of monocytes in bipolar disorder (BD) patients in the absence/presence of lithium. Methods: Monocytes of outpatients with DSM-IV BD (n = 80, of whom 64 were lithium-treated) and of healthy control subjects (n = 59) were cultured in vitro and exposed (24 h) or not exposed to lipopolysaccharide (LPS) and/or graded concentrations of lithium chloride (LiCl). IL-1 β and IL-6 production was assessed by enzyme-linked immunosorbent assay (ELISA) (supernatants). Results: Monocytes stimulated by LPS from non-lithium-treated bipolar patients were characterized by an abnormal IL-1 β/IL-6 production ratio, i.e., low IL-1 β and high IL-6 production. Lithium treatment increased IL-1 β and decreased IL-6 production and thus restored the aberrant ratio. In vitro exposure of monocytes to LiCl did not have the same effects as lithium treatment: the procedure decreased IL-1 β production and had minimal effects on IL-6 production. Conclusions: Blood monocytes have an altered proinflammatory status in BD. Lithium treatment restores this altered status. Short-term in vitro exposure of monocytes to lithium has other effects than lithium treatment. [ABSTRACT FROM AUTHOR]

Glutamic acid decarboxylase ( GAD) is a major inhibitory neurotransmitter in the brain, which catalyses the reaction of l-glutamate to γ-aminobutyric acid. There are two isoforms of GAD, a 65-kDa form and a 67-kDa form, which are encoded by two different genes. As previous studies suggested a role for GAD67 splice variants during fetal pancreas development, we have investigated the mRNA expression of GAD67 and GAD67 splice variants in a series of 14 human fetal pancreases between 14 weeks gestation and term and in adult control pancreases by RT-PCR. In this study, we demonstrate mRNA expression of GAD67 and four GAD67 splice variants, including GAD25, in human fetal and adult specimens. Some of the splice variants, including various proportions of exon 7 or a new exon between exons 6 and 7, have not been described before in the human pancreas. We speculate that the expression of these GAD67 splice variants might be related to human fetal pancreas development. [ABSTRACT FROM AUTHOR]

Objective: A relative resistance of immune cells to steroids has been established in patients with major depression (MD). In this study, we investigated the in vitro responsiveness of T cells to dexamethasone (DEX) of patients with bipolar disorder (BD). Methods: T cells of outpatients with DSM-IV BD (n = 54) and of healthy control subjects (HC; n = 29) were isolated, cultured and stimulated with phytohemagglutinin (PHA) for 72 h. The suppressive effect of graded concentrations of DEX (5 × 10−9–10−5 M) on PHA-induced CD25 (IL-2R) expression was measured by fluorescence-activated cell sorting (FACS) analysis. Data were correlated to the T-cell activation status in the peripheral blood of the same patients and to their diagnosis, current mood state, ultradian cycling pattern and current use of medication, including lithium. Results: T cells of patients with BD were less sensitive to DEX-induced suppressive effects as compared with T cells of HC. These data were particularly evident at 10−7 M DEX (mean % suppression ± SEM BD: 18.9% ± 3.5 versus HC: 35.8% ± 4.7, p = 0.001). We found no correlations of this relative in vitro DEX resistance of T cells neither with the previously mentioned clinical characteristics nor with the actual activation status of the T cells in the BD patients. Conclusion: A relative T-cell resistance to steroids, as has been observed in MD previously, may be a trait phenomenon of BD, independent of mood state. [ABSTRACT FROM AUTHOR]

Previously, we reported elevated numbers of macrophages in the pancreas of NOD mice, a spontaneous animal model for T1D, during the early postnatal period. Extracellular matrix plays an important role in the tissue trafficking and retention of macrophages as well as in postnatal pancreas development. Therefore, we have examined the expression and distribution of laminin and fibronectin, two major extracellular matrix proteins and their corresponding integrin receptors, in the pre-weaning pancreases of NOD mice and control mouse strains. In addition, we have characterized the pancreas morphology during this period, since the morphology of the pre-weaning pancreas before the onset of lymphocytic peri-insulitis, when the pancreas is still subject to developmental changes, has been poorly documented. We show that laminin labeling is mainly associated with exocrine tissue, whereas fibronectin labeling was mostly localized at the islet-ductal pole, islet periphery and in intralobular septa. Moreover, the protein expression level of fibronectin was increased in NOD pancreases at the early stage of postnatal development, as compared to pancreases of C57BL/6 and BALB/c mouse strains. Interestingly, pancreatic macrophages were essentially found at sites of intense fibronectin labeling. The increased fibronectin content in NOD neonatal pancreas coincided with altered islet morphology, histologically reflected by enlarged and irregular shaped islets and increased percentages of total endocrine area as compared to that of control strains. In conclusion, increased levels of the extracellular matrix protein fibronectin were found in the early postnatal NOD pancreas, and this is associated with an enhanced accumulation of macrophages and altered islet morphology. [ABSTRACT FROM AUTHOR]

The recruitment of monocytes from the bloodstream is crucial in the accumulation of macrophages and dendritic cells in type 1 diabetic pancreases. Adhesion via integrins to endothelium and extracellular matrix proteins, such as fibronectin (FN), and the production of myeloid-related protein (MRP)-8, -14, and -8/14 by recently transmigrated monocytes are thought to be instrumental in such recruitment. We determined the FN-adhesive capacity and integrin expression of monocytes of type 1 and type 2 diabetic patients and related them to the subjects' serum levels of MRP-8, -14 and -8/14. Monocytes of type 1 diabetic patients displayed an increased adhesion to fibronectin in comparison with type 2 patients and healthy control subjects but had a normal expression of the FN binding integrins CD29, CD49a, CD49d, and CD49e (although CD11b and CD18 expression was increased). MRP-8/14, which was increased in the sera of type 1 diabetic patients, induced healthy donor monocytes to adhere to FN and upregulate CD11b expression in a dosage-dependent manner. The observed MRP-induced increased adhesion of monocytes to FN and upregulation of CD11b most likely contributed to a facilitated accumulation of monocytes and monocyte-derived cells at the site of inflammation, in this case the pancreatic islets. [ABSTRACT FROM AUTHOR]

Macrophages (MΦs), dendritic cells (DCs) and lymphocytes are involved in the pathogenesis of type 1 diabetes (T1D). However, the presence of these cells is not specific for a diabetes-prone background. MΦs are also constituents of the normal fetal, neonatal and adult pancreas. We hypothesize that MΦs, DCs and lymphocytes have a role in pancreas and islet development because immune cells (particularly MΦs) are known to participate in the morphogenesis of various organs. In addition, we hypothesize that a defective function of immune cells generates an aberrant islet morphogenesis in T1D-prone individuals or animals. In the post-weaning period (a period of islet remodelling), the same defective function of immune cells might precipitate the pro-inflammatory peri-islet microenvironment that favours islet autoimmune reactivity. [Copyright &y& Elsevier]

We investigated the prospective relationship between thyroid status and the risk of dementia and Alzheimer's disease among a random sample of 1843 participants, aged 55 years and over, from the population-based prospective Rotterdam Study. Thyroid status was measured at baseline (1990–93), through assessment of serum antibodies to thyroid peroxidase (TPO-Abs, positive: >10 IU/ml), serum TSH levels, and when TSH was abnormal (<0·4 or >4·0 mU/l), serum thyroxin levels (T4). At baseline and at follow up, after on average 2 years, participants were screened for dementia. Diagnoses were based on international criteria. Persons with reduced TSH levels at baseline had a more than threefold increased risk of dementia (RR = 3·5, 95%CI: 1·2–10·0) and of Alzheimer's disease (RR = 3·5, 95%CI: 1·1–11·5), after adjustment for age and sex. Among persons with reduced TSH levels, T4 levels appeared to be positively related to the risk of dementia (RR per SD increase = 2·9, 95%CI: 0·7–12·2), although none of those who became demented had a T4 level above the normal range (>140 nmol/l). The risk of dementia was especially increased in subjects with low TSH who were positive for TPO-Abs (RR = 23·7, 95%CI: 4·0–140). This is the first prospective study to suggest that subclinical hyperthyroidism in the elderly increases the risk of dementia and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The number of blood monocytes, their ability to mature into macrophages, their NBT-dye reduction capacity and their migration towards casein were studied in 29 patients with squamous cell carcinoma of the larynx, 12 patients with squamous cell carcinoma at other sites within the head and neck and two groups of male controls, one of 29.7 yrs. ± 7.2 (SD) and the other of 71.4 yrs ± 6.8 (SD). An age dependency of monocyte function in healthy individuals was established. Increased numbers of monocytes per ml blood were found in the older men. These cells showed an enhanced migration toward casein. Their maturation capacity was decreased. A clear impairment of migration toward casein was found in the two groups of carcinoma patients. The number of monocytes was only marginally affected. The maturation was found to be enhanced. An impaired recruitment of mononuclear phagocytes at the site of malignant growth due to diminished migratory capacities might be important for failing immune surveillance. [ABSTRACT FROM AUTHOR]

In earlier experiments chemotactic responsiveness of peripheral blood monocytes obtained from patients with head and neck cancers was found to be markedly depressed. In an attempt to attribute this defect in migration to an influence excited by low molecular weight factors of less than 25,000 daltons, derived from the tumor, Amicon filtrates of head and neck cancer cells were administered sub-cutaneously to C3H mice 24 hrs. before the intraperitoneal injection of concanavelin A. Subsequent macrophage accumulation into the peritoneal cavity was quantified. A clear inhibition of macrophage infiltration was found, particularly when filtrates of poorly differentiated tumors were used. Injection of filtrates from healthy oral mucosa were negative, whereas mouse mammary carcinoma filtrates strongly inhibited accumulation. [ABSTRACT FROM AUTHOR]

In this issue of BBI Melbourne et al describe a reduced activity of the JAK-STAT1 pathway in leukocytes of early and acute schizophrenia patients. This editorial discusses the report of Melbourne et al as being in accord with the view that active forms of schizophrenia are characterized by a de-activation of the Th1 driven M1/JAK-STAT1 mediated pro-inflammatory pathway in myeloid cells (macrophages, dendritic cells and microglia). Myeloid cells can be inflammatory activated and de-activated via various different molecular pathways (leading to various types of macrophages, such as e.g. various M1, various M2 and atherosclerosis related macrophages). There are data in the literature that pathways related to the Th17 driven MAP-kinase pro-inflammatory M1 pathway are activated in the myeloid cells of early and acute schizophrenia. The question thus arises what the intracellular molecular processes are which drive the complex inflammatory set points of macrophages and microglia in early and acute forms of schizophrenia. [ABSTRACT FROM AUTHOR]