Effect of acute and repeated treatment with mirtazapine on the immunity of noradrenaline transporter knockout C57BL/6J mice

Kubera, Marta; Román, Ádám; Basta‐Kaim, Agnieszka; Budziszewska, Bogusława; Zajı́cová, Alena; Holáň, Vladimı́r; Rogóż, Z; Skuza, G; Leśkiewicz, Monika; Regulska, Magdalena; Jagła, Grzegorz; Nowak, Wojciech; Lasoń, Władysław

doi:10.1016/j.pbb.2006.11.017

Cited by 13 publications

(8 citation statements)

References 28 publications

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“…Mirtazapine is a tetracyclic piperazinoazepine that exhibits a complex pharmacology, having both central and peripheral effects (29). Specifically, mirtazapine acts as a 5HT2 A receptor antagonist, 5HT2 C receptor inverse agonist, and an antagonist for 5HT 3 and histamine (H1) receptors (29,30). Therefore, in keeping with its wide range of receptor activity, mirtazapine has been increasingly used clinically to treat a broad range of symptoms including depression, anxiety, and insomnia (29).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, in keeping with its wide range of receptor activity, mirtazapine has been increasingly used clinically to treat a broad range of symptoms including depression, anxiety, and insomnia ( 29 ). However, in addition to its effects on symptoms, there is evidence that mirtazapine also affects systemic ( 30 – 32 ) and hepatic ( 12 , 33 ) immunity.…”

Section: Discussionmentioning

confidence: 99%

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The Antidepressant Mirtazapine Activates Hepatic Macrophages, Facilitating Pathogen Clearance While Limiting Tissue Damage in Mice

et al. 2020

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Background and Aims: Mirtazapine is an atypical antidepressant with antagonist activity for serotonin and histamine receptors. Clinical and experimental evidence suggests that, in addition to treating depression, mirtazapine also alters liver innate immunity and suppresses immune-driven hepatic macrophage activation. Liver macrophages, Kupffer cells, represent the largest collection of fixed macrophages in the body and are critical in regulating hepatic immunity. In addition to their capacity to regulate inflammation, Kupffer cells are key sentinels for clearing blood-borne pathogens, preventing their dissemination within the body. This process involves pathogen capture, phagocytosis, and activation-induced killing via reactive oxygen species (ROS) production. Therefore, we speculated that mirtazapine might adversely alter Kupffer cell pathogen-associated activation and killing. Methods: Mice were treated with mirtazapine and time-dependent changes in Kupffer cells were characterized using intravital microscopy. Macrophage and neutrophil responses, bacterial dissemination, and liver damage were assessed following i.v. infection with a pathogenic strain of S. aureus. Results: Mirtazapine rapidly (within 1.5 h) activates Kupffer cells, indicated by a loss of elongated shape with cellular rounding. However, this shape change did not result in impaired pathogen capture function, and, in fact, generated enhanced ROS production in response to S. aureus-induced sepsis. Neutrophil dynamics were altered with reduced cellular recruitment to the liver following infection. Bacterial dissemination postintravenous administration was not altered by mirtazapine treatment; however, hepatic abscess formation was significantly reduced. Conclusions: Mirtazapine rapidly activates Kupffer cells, associated with preserved bacterial capture functions and enhanced ROS generation capacity. Moreover, these changes in Kupffer cells were linked to a beneficial reduction in hepatic abscess size. In

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Antidepressant Mirtazapine Activates Hepatic Macrophages, Facilitating Pathogen Clearance While Limiting Tissue Damage in Mice

et al. 2020

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“…The plasma levels of TNF-α and soluble TNF receptors are increased in patients with major depressive disorders treated with mirtazapine [36]. With norepinephrine transporter knockout mice, Kubera et al found that the decrease of IL-6 and IFN-γ, and the increase of IL-4 production may be due to the increase of norepinephrine level in the spleen after mirtazapine treatment [37]. On the other hand, IFN-γ-indoleamine 2,3-dioxygenase (IDO) axis also has been reported to regulate the sIL-12-mediated antitumor immunity [28], in which IFN-γ is the main cytokine induced by sIL-12 and plays a critical role to its antitumor effects [38].…”

Section: Discussionmentioning

confidence: 99%

Mirtazapine Inhibits Tumor Growth via Immune Response and Serotonergic System

et al. 2012

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To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug) and drug (mirtazapine), and four groups with tumors, i.e. never (no drug), always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment), concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment), and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment). The “psychiatric” conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interlukin-12 (sIL-12) and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after) as compared with that of never. In addition, interferon-γ level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-α (TNF-α) expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [123I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level.

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“…As has been shown for other treatment strategies, mirtazapine at least partially reverses changes in immunity associated with depression. 56 Studies investigating the direct interactions between mirtazapine and the immune system led to somewhat contradictory results of in vivo and in vitro experiments, 186,187 thus not allowing clear conclusions at this point.…”

Section: Mirtazapine In Ibdmentioning

confidence: 99%

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD

Thorkelson

Bielefeldt

Szigethy

2016

Inflammatory Bowel Diseases

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Antidepressant medications are frequently prescribed for depression, anxiety disorders, and chronic pain syndromes, but overall support for their efficacy is modest at best. Psychological interventions have growing support for having much more robust effects without the side effects of antidepressants and should be considered first-line treatment or at least an adjunct to psychotropic medications for these conditions.

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Effect of acute and repeated treatment with mirtazapine on the immunity of noradrenaline transporter knockout C57BL/6J mice

Cited by 13 publications

References 28 publications

The Antidepressant Mirtazapine Activates Hepatic Macrophages, Facilitating Pathogen Clearance While Limiting Tissue Damage in Mice

The Antidepressant Mirtazapine Activates Hepatic Macrophages, Facilitating Pathogen Clearance While Limiting Tissue Damage in Mice

Mirtazapine Inhibits Tumor Growth via Immune Response and Serotonergic System

Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD

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