Attenuated inflammatory response of monocyte-derived macrophage from patients with BD: a preliminary report

Ascoli, Bruna Maria; Parisi, Mariana Migliorini; Bristot, Giovana; Antqueviezc, Bárbara; Géa, Luíza Paul; Colombo, Rafael; Kapczinski, Flávio; Guma, Fátima Theresinha Costa Rodrigues; Brietzke, Elisa; Barbé-Tuana, Florencia Marı́a; Rosa, Adriane Ribeiro

doi:10.1186/s40345-019-0148-x

Cited by 19 publications

(27 citation statements)

References 62 publications

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“…It is important to note that these cells were not stimulated, so their results only provide insight as to their behavior at rest. A recent study by Ascoli et al (2019) found that inflammatory macrophage responses after M1/M2 skewing diminished with disease progression in BD, where "early stage" BD macrophages more closely resembled HC macrophage responses, but in later-stage disease the responses were attenuated. Our patients were not considered chronically ill, all were within a year of first symptoms and our findings that macrophages in the AFF group respond similarly to HC after LPS and M1 stimulation supports this research.…”

Section: Discussionmentioning

confidence: 95%

Differential Macrophage Responses in Affective Versus Non-Affective First-Episode Psychosis Patients

Hughes

Mills-Ko

Yang

et al. 2021

Front. Cell. Neurosci.

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Increased innate immune activation and inflammation are common findings in psychotic and affective (mood) disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), including increased numbers and activation of monocytes and macrophages. These findings often differ depending on the disorder, for example, we previously found increases in circulating inflammatory cytokines associated with monocytes and macrophages in SCZ, while BD had increases in anti-inflammatory cytokines. Despite these differences, few studies have specifically compared immune dysfunction in affective versus non-affective psychotic disorders and none have compared functional monocyte responses across these disorders. To address this, we recruited 25 first episode psychosis (FEP) patients and 23 healthy controls (HC). FEP patients were further grouped based on the presence (AFF) or absence (NON) of mood disorder. We isolated peripheral blood mononuclear cells and cultured them for 1 week with M-CSF to obtain monocyte-derived macrophages. These cells were then stimulated for 24 h to skew them to inflammatory and alternative phenotypes, in order to identify differences in these responses. Following stimulation with LPS and LPS plus IFNγ, we found that macrophages from the NON-group had diminished inflammatory responses compared to both HC and AFF groups. Interestingly, when skewing macrophages to an alternative phenotype using LPS plus IL-4, the AFF macrophages increased production of inflammatory cytokines. Receiver operating curve analysis showed predictive power of inflammatory cytokine concentrations after LPS stimulation in the AFF group versus NON-group. Our results suggest dysfunctional monocyte responses in both affective and non-affective psychotic disorder, with varying types of immune dysfunction depending on the presence or absence of a mood component.

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Section: Discussionmentioning

confidence: 95%

Differential Macrophage Responses in Affective Versus Non-Affective First-Episode Psychosis Patients

Hughes

Mills-Ko

Yang

et al. 2021

Front. Cell. Neurosci.

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“…The identified flaw in the control of immune system functioning might be connected to the involvement of so many bodily systems with the advancement of the diathesis in BD. 36 A meta-analytic review investigated the likelihood of determining a biomarker signature of illness phase in BD. In the analysis, 53 studies comprising 2467 cases and 2360 controls were included and it showed that in BD hs-CRP, IL-6, BDNF, TNF-α, and soluble TNF-α receptor 1 could discriminate a distinctive affective exacerbation.…”

Section: Inflammatory Biomarkersmentioning

confidence: 99%

The Discovery of Clinically Applicable Biomarkers for Bipolar Disorder: A Review of Candidate and Proteomic Approaches

Muneer

2020

Chonnam Med J

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Bipolar disorder (BD) is a severe psychiatric condition which affects innumerable people across the globe. The etiopathogenesis of BD is multi-faceted with genetic, environmental and psychosocial factors playing a role. Hitherto, the diagnosis and management of BD are purely on empirical grounds as we lack confirmed biomarkers for this condition. In this regard, hypothesis-driven investigations have been unable to identify clinically applicable biomarkers, steering the field towards newer technologies. Innovative, state-of-the-art techniques like multiplex immunoassays and mass spectrometry can potentially investigate the entire proteome. By detecting up or down regulated proteins, novel biomarkers are identified and new postulates about the etiopathogenesis of BD are specified. Hence, biological pathways are uncovered which are involved in the initiation and advancement of the disease and new therapeutic targets are identified. In this manuscript, the extant literature is thoroughly reviewed and the latest findings on candidate BD biomarkers are provided, followed by an overview of the proteomic approaches. It was found that due to the heterogeneous nature of BD no single biomarker is feasible, instead a panel of tests is more likely to be useful. With the application of latest technologies, it is expected that validated biomarkers will be discovered which will be useful as diagnostic tools and help in the delivery of individually tailored therapies to the patients.

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“…В настоящее время БАР рассматривают как мультисистемное заболевание, так как оно часто ассоциируется с коморбидными системными воспалительными заболеваниями, такими как сердечно-сосудистые заболевания, абдоминальное ожирение, инсулинорезистентность, аутоиммунные расстройства, которые, как показано, ассоциированы с ранними проявлениями этого заболевания [45][46][47][48]. Существует большое количество исследований, свидетельствующих о дисфункции иммунного ответа, вовлеченного в патогенез БАР [8, 48,49], а именно, сообщается, что БАР сопровождается провоспалительной активацией иммунитета. При этом для депрессии характерна повышенная активность ряда провоспалительных цитокинов, в частности IL-1b, IL-6, TNF-[7, 24, 50-52], а также растворимых рецепторов к ним [52].…”

Section: моноциты и барunclassified

“…Было высказано предположение, что воспаление, включающее изменения уровней воспалительных цитокинов, кортикостероидов, активности окислительного стресса и изменение нейрогенеза, является одной из причин, способной объяснить некоторые клинические особенности БАР [50], которые, по мнению авторов, включают прогрессирующее укорочение интервалов между эпизодами с каждым новым рецидивом заболевания. Действительно, по сообщениям некоторых авторов, увеличение продолжительности болезни и количества маниакальных и депрессивных эпизодов повышают риск развития соматических сопутствующих заболеваний, особенно связанных с метаболической и иммунной дисфункцией, при этом депрессия связана с риском развития, например сердечно-сосудистых заболеваний, инсульта, диабета и ожирения [48]. Было показано, что повышенная секреция цитокинов IL-1 , TNF-, IL-6 у больных БАР по сравнению со здоровыми людьми выявлялась на ранних стадиях болезни [22], тогда как по мере прогрессирования заболевания секреция цитокинов значительно снижалась [48].…”

Section: моноциты и барunclassified

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 2

Vasilyeva¹,

Брусов²

2020

Psychiatry

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Introduction: at the end of the last century, the macrophage-T-lymphocyte theory of the development of mental disorders was formulated. It underlines the important role of monocytes/macrophages and cytokines produced by them in the pathogenesis of schizophrenia, bipolar affective disorder (BAD) and depression. The first part of our review is dedicated to the analysis of the mechanisms of cellular and molecular interactions of activated monocytes/macrophages synthesizing proinflammatory CD16 receptors with endothelial cells, platelets, and microglia cells in the pathogenesis of systemic immune inflammation, including CNS as a result of violation of the integrity of the blood-brain barrier (BBB), activate microglia and cause the development of neuroinflammation in patients.The aim of work: to analyze and summarize the results of the main scientific publications for the role of cell-molecular mechanisms of the monocyte-macrophage immunity link activation in the pathogenesis of schizophrenia, BAD and depression. Material and methods: keywords “proinflammatory monocytes, cytokines, chemokines, molecules of cell adhesion, microglia, neuroinflammation, mental disorders” were used to search for data published over the past 20 years in domestic and foreign studies in PubMed, eLIBRARY, Science direct and EMBASE.Conclusion: the present review is dedicated to the analysis of the latest research data concerning an increase in the number of active circulating monocytes/macrophages and an increased level of proinflammatory cytokines, chemokines and receptors for them produced by monocytes in patients with schizophrenia, BAD and depression, what allows to associate these disorders with systemic immune inflammation. The data reasearches on cellular and molecular mechanisms of proinflammatory monocytes/macrophages interaction with microglia cells that initiate neuroinflammation in the CNS and lead to destabilization of brain function and the development of psychotic disorders are presented. The association of high levels of proinflammatory cytokines with somatic comorbidity, including metabolic syndrome, diabetes, atherosclerosis and other systemic diseases is shown in patients with mental disorders.Findings: the presented review of the research data allows us to better understand the cellular and molecular aspects of activation of the monocyte-macrophage immunity link in the development of neuroinflammation and cognitive decline in the pathogenesis of mental disorders, as well as helps in the search for informative biomarkers of the positive treatment of these disorders and the new approaches in the treatment of patients, based on the complex use of psychotropic and anti-inflammatory drugs.

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Attenuated inflammatory response of monocyte-derived macrophage from patients with BD: a preliminary report

Cited by 19 publications

References 62 publications

Differential Macrophage Responses in Affective Versus Non-Affective First-Episode Psychosis Patients

Differential Macrophage Responses in Affective Versus Non-Affective First-Episode Psychosis Patients

The Discovery of Clinically Applicable Biomarkers for Bipolar Disorder: A Review of Candidate and Proteomic Approaches

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 2

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