Association Between Enhanced Soluble CD40 Ligand and Proinflammatory and Prothrombotic States in Major Depressive Disorder

Leo, Roberto; Lorenzo, Giorgio Di; Tesauro, Manfredi; Razzini, Cinzia; Forleo, Giovanni B.; Chiricolo, Gaetano; Cola, Clarissa; Zanasi, Marco; Troisi, Alfonso; Siracusano, Alberto; Lauro, Renato; Romeo, Francesco

doi:10.4088/jcp.v67n1114

Cited by 96 publications

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“…CD40AB-induced SBS is TNFdependent, as evidenced by its absence in TNF receptor-1 knockout mice and its prevention in mice co-injected with the TNF blocker etanercept (Gast et al, 2013;Taraborrelli et al, 2011). The potential utility of this mouse model for the study of the relationship between immuneinflammation and MDD is evidenced by reports that MDD patients, compared to control subjects, have high blood levels of CD40 (Neubauer et al, 2013), soluble CD40L (Leo et al, 2006;Neubauer et al, 2013), TNF (Dowlati et al, 2010), IDO and KYN (Kim et al, 2012), and by the evidence that improved mood in MDD patients co-occurred with reduced blood levels of soluble CD40L (Leo et al, 2006;Selzhammer et al, 2013).…”

Section: Including Tumor Necrosis Factor (Tnf) Interleukin-(il-) Il-mentioning

confidence: 99%

CD40-TNF activation in mice induces extended sickness behavior syndrome co-incident with but not dependent on activation of the kynurenine pathway

Cathomas

Fuertig

Sigrist

et al. 2015

Brain, Behavior, and Immunity

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The similarity between sickness behavior syndrome (SBS) in infection and autoimmune disorders and certain symptoms in major depressive disorder (MDD), and the high co-morbidity of autoimmune disorders and MDD, constitutes some of the major evidence for the immune-inflammation hypothesis of MDD. CD40 ligand-CD40 immune-activation is important in host response to infection and in development of autoimmunity. Mice given a single intra-peritoneal injection of CD40 agonist antibody (CD40AB) develop SBS for 2-3days characterized by weight loss and increased sleep, effects that are dependent on the cytokine, tumor necrosis factor (TNF). Here we report that CD40AB also induces behavioral effects that extend beyond acute SBS and co-occur with but are not mediated by kynurenine pathway activation and recovery. CD40AB led to decreased saccharin drinking (days 1-7) and decreased Pavlovian fear conditioning (days 5-6), and was without effect on physical fatigue (day 5). These behavioral effects co-occurred with increased plasma and brain levels of kynurenine and its metabolites (days 1-7/8). Co-injection of TNF blocker etanercept with CD40AB prevented each of SBS, reduced saccharin drinking, and kynurenine pathway activation in plasma and brain. Repeated oral administration of a selective indoleamine 2,3-dioxygenase (IDO) inhibitor blocked activation of the kynurenine pathway but was without effect on SBS and saccharin drinking. This study provides novel evidence that CD40-TNF activation induces deficits in saccharin drinking and Pavlovian fear learning and activates the kynurenine pathway, and that CD40-TNF activation of the kynurenine pathway is not necessary for induction of the acute or extended SBS effects. AbstractThe similarity between sickness behavior syndrome (SBS) in infection and autoimmune disorders and certain symptoms in major depressive disorder (MDD), and the high co-morbidity of autoimmune disorders and MDD, constitutes some of the major evidence for the immuneinflammation hypothesis of MDD. CD40 ligand-CD40 immune-activation is important in host response to infection and in development of autoimmunity. Mice given a single intra-peritoneal injection of CD40 agonist antibody (CD40AB) develop SBS for 2-3 days characterized by weight loss and increased sleep, effects that are dependent on the cytokine, tumor necrosis factor (TNF). Here we report that CD40AB also induces behavioral effects that extend beyond acute SBS and co-occur with but are not mediated by kynurenine pathway activation and recovery. CD40AB led to decreased saccharin drinking (days 1-7) and decreased Pavlovian fear conditioning (days 5-6), and was without effect on physical fatigue (day 5). These behavioral effects co-occurred with increased plasma and brain levels of kynurenine and its metabolites (days 1-7/8). Co-injection of TNF blocker etanercept with CD40AB prevented each of SBS, reduced saccharin drinking, and kynurenine pathway activation in plasma and brain. Repeated oral administration of a selective indoleamine 2,3-dioxyg...

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Section: Including Tumor Necrosis Factor (Tnf) Interleukin-(il-) Il-mentioning

confidence: 99%

CD40-TNF activation in mice induces extended sickness behavior syndrome co-incident with but not dependent on activation of the kynurenine pathway

Cathomas

Fuertig

Sigrist

et al. 2015

Brain, Behavior, and Immunity

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“…Mice with neutralization of this ligand-receptor pathway are protected from experimental autoimmune diseases such as experimental autoimmune encephalitis (EAE). Moreover patients with depression have increased plasma levels of soluble CD40 and CD40L (Leo et al, 2006;Neubauer et al, 2013). CD40L is expressed mainly by activated CD4+ T cells and binds to CD40 expressed on macrophages, B-lymphocytes and dendritic cells.…”

Section: Activation Of Cd40 Leads To Depression-like Behavior In Micementioning

confidence: 99%

Depression in Autoimmune Diseases

Pryce

Fontana

2016

Current Topics in Behavioral Neurosciences

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Up to 50% of patients with autoimmune diseases show an impairment of health-related quality of life and exhibit depression-like symptoms. The immune system not only leads to inflammation in affected organs, but also mediates behavior abnormalities including fatigue and depression-like symptoms. This review focuses on the different pathways involved in the communication of the immune system with the neuronal network and the body's timing system. The latter is built up by a hierarchically organized expression of clock genes. As discussed here, the activation of the immune system interferes with high amplitude expression of clock genes, an effect which may play a pivotal role in depression-like behavior in autoimmune diseases.

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“…43 Depression and anxiety affect biological processes of cardiovascular function in patients with heart failure by altering neurohormonal function via activation of the hypothalamic-pituitary-adrenal (HPA) axis, 44,45 autonomic dysregulation, 46,47 and activation of cytokine cascades and platelets. [48][49][50] Conversely, neurohormonal dysfunctions due to heart failure may increase the risk for depression and anxiety in patients with this cardiovascular abnormality. [44][45][46][47]51,52 …”

Section: Biopsychosocial Holistic Model Of Cardiovascular Healthmentioning

confidence: 99%

“…[48][49][50] In heart failure, through a complex process that includes a cascade of neurohormones, activated platelets interact with leukocytes to adhere to endothelial cells in the vasculature and promote thrombosis. 95 Through stimulation of platelet receptors for norepine phrine and epinephrine, elevated levels of circulating cate cholamines potentiate platelet responses.…”

Section: Platelet Activationmentioning

confidence: 99%

Pathophysiological Relationships Between Heart Failure and Depression and Anxiety

Chapa

Akintade

Son

et al. 2014

Critical Care Nurse

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H eart failure is an epidemic with national and global implications. Compared with the situation in other cardiac diseases, the incidence and prevalence of heart failure continue to increase despite recent advancements in understanding and treatment. Increased survival after myocardial infarction, aging of the population, and increased incidence of diabetes are contributing factors. This article has been designated for CNE credit. A closed-book, multiple-choice examination follows this article, which tests your knowledge of the following objectives:1. Describe the biopsychosocial holistic model for cardiovascular health 2. Identify 2 neurohormonal pathways and their impact in heart failure 3. Identify nursing implications for heart failure, depression, and anxiety CNE Continuing Nursing EducationCover Depression and anxiety are common comorbid conditions in patients with heart failure. Patients with heart failure and depression have increased mortality. The association of anxiety with increased mortality in patients with heart failure is not established. The purpose of this article is to illustrate the similarities of the underlying pathophysiology of heart failure, depression, and anxiety by using the Biopsychosocial Holistic Model of Cardiovascular Health. Depression and anxiety affect biological processes of cardiovascular function in patients with heart failure by altering neurohormonal function via activation of the hypothalamic-pituitary-adrenal axis, autonomic dysregulation, and activation of cytokine cascades and platelets. Patients with heart failure and depression or anxiety may exhibit a continued cycle of heart failure progression, increased depression, and increased anxiety. Understanding the underlying pathophysiological relationships in patients with heart failure who experience comorbid depression and/or anxiety is critical in order to implement appropriate treatments, educate patients and caregivers, and educate other health professionals. (Critical Care Nurse. 2014;34[2]:14-25)

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Association Between Enhanced Soluble CD40 Ligand and Proinflammatory and Prothrombotic States in Major Depressive Disorder

Cited by 96 publications

References 0 publications

CD40-TNF activation in mice induces extended sickness behavior syndrome co-incident with but not dependent on activation of the kynurenine pathway

CD40-TNF activation in mice induces extended sickness behavior syndrome co-incident with but not dependent on activation of the kynurenine pathway

Depression in Autoimmune Diseases

Pathophysiological Relationships Between Heart Failure and Depression and Anxiety

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