Unmetabolized quetiapine exerts an in vitro effect on innate immune cells by modulating inflammatory response and neutrophil extracellular trap formation

Turra, Bárbara Osmarin; Barbisan, Fernanda; Azzolin, Verônica Farina; Teixeira, Cibele Ferreira; Flores, Thamara Graziela; Braun, Luiza Elisabete; Nerys, Daniel Augusto de Oliveira; Rissi, Vitor Braga; Alves, Audrei de Oliveira; Assmann, Charles Elias; Jung, Ivo Emilio da Cruz; Marques, Liana Pinheiro Santos; Cruz, Ivana Beatrice Mânica da

doi:10.1016/j.biopha.2020.110497

Cited by 11 publications

(6 citation statements)

References 63 publications

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“…A study on mice showed that quetiapine increased serum levels of IL-10 and decreased IFN-γ 4 h after intraperitoneal injection of lipopolysaccharide, with similar results observed within the brain [ 38 ]. Unmetabolized quetiapine was also shown to increase levels of oxidative molecules (nitric oxide), protein levels, and proinflammatory cytokines (IL-α, IL-6, and TNF-α) in the in vitro setting [ 39 ].…”

Section: The Interrelation Between Sleep and Alterations In Inflammat...mentioning

confidence: 99%

Potential Role of Sleep Deficiency in Inducing Immune Dysfunction

et al. 2022

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Sleep deficiency and insomnia deteriorate the quality of patients’ lives, yet the exact influence of these factors on the immune system has only begun to gain interest in recent years. Growing evidence shows that insomnia is a risk factor for numerous diseases, including common infections and autoimmune diseases. Levels of inflammatory markers also seem to be abnormal in sleep deficient individuals, which may lead to low-grade inflammation. The interpretation of studies is difficult due to the equivocal term “sleep disturbances,” as well as due to the various criteria used in studies. This narrative review aims to summarize the available knowledge regarding the bidirectional influence of the immune system and sleep disturbances.

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Section: The Interrelation Between Sleep and Alterations In Inflammat...mentioning

confidence: 99%

Potential Role of Sleep Deficiency in Inducing Immune Dysfunction

et al. 2022

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“…A new study on the in vitro impact of unmetabolized quetiapine on innate immune cells has shown that unmetabolized quetiapine increases formation of NETs via activated neutrophils. These results confirm the impact of quetiapine on neutrophil function, which may aggravate NETs formation and pulmonary epithelial cell damage during severe SARS-CoV-2 infection [13]. In contrast, researchers have not found any similar action in neutrophils exposed to antipsychotic clozapine [4].…”

Section: Dear Editormentioning

confidence: 52%

“…Hence, the use of NETosis stimulants can exacerbate pulmonary epithelial cell damage among COVID-19 patients [2,3]. Recently, the effect of two common second-generation antipsychotic drugs, namely quetiapine and clozapine, has been investigated on innate immune cells [4,13]. A new study on the in vitro impact of unmetabolized quetiapine on innate immune cells has shown that unmetabolized quetiapine increases formation of NETs via activated neutrophils.…”

Section: Dear Editormentioning

confidence: 99%

Quetiapine versus Clozapine in Treating Psychiatric Patients with Severe COVID-19: A Netosis-Based Opinion

Khosravi

2021

ELECTRON J GEN MED

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“…For example, in nonactivated conditions, this drug triggered a consistent inflammatory response (including a high level of NO, proinflammatory gene expression and diminished level of IL-10). In contrast, after stimulation, the effects of quetiapine revealed an anti-inflammatory profile [ 110 ]. This finding points to its immunomodulatory potential, which was also observed in clinical studies in first-episode psychosis patients [ 111 ].…”

Section: Discussionmentioning

confidence: 99%

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Chamera

Curzytek

Kamińska

et al. 2022

Cells

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The maternal immune activation produced by the systemic administration of lipopolysaccharide (LPS) in rats provides valuable insights into the basis of behavioural schizophrenia-like disturbances and biochemical changes in the brains of the offspring, such as microglial activation. Regarding therapy, antipsychotics continually constitute the cornerstone of schizophrenia treatment. To their various efficacy and side effects, as well as not fully recognised mechanisms of action, further characteristics have been suggested, including an anti-inflammatory action via the impact on neuron–microglia axes responsible for inhibition of microglial activation. Therefore, in the present study, we sought to determine whether chronic treatment with chlorpromazine, quetiapine or aripiprazole could influence schizophrenia-like behavioural disturbances at the level of sensorimotor gating in male offspring prenatally exposed to LPS. Simultaneously, we wanted to explore if the chosen antipsychotics display a positive impact on the neuroimmunological parameters in the brains of these adult animals with a special focus on the ligand-receptor axes controlling neuron–microglia communication as well as pro- and anti-inflammatory factors related to the microglial activity. The results of our research revealed the beneficial effect of quetiapine on deficits in sensorimotor gating observed in prenatally LPS-exposed offspring. In terms of axes controlling neuron–microglia communication and markers of microglial reactivity, we observed a subtle impact of quetiapine on hippocampal Cx3cl1 and Cx3cr1 levels, as well as cortical Cd68 expression. Hence, further research is required to fully define and explain the involvement of quetiapine and other antipsychotics in Cx3cl1-Cx3cr1 and/or Cd200-Cd200r axes modulation and inflammatory processes in the LPS-based model of schizophrenia-like disturbances.

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Unmetabolized quetiapine exerts an in vitro effect on innate immune cells by modulating inflammatory response and neutrophil extracellular trap formation

Cited by 11 publications

References 63 publications

Potential Role of Sleep Deficiency in Inducing Immune Dysfunction

Potential Role of Sleep Deficiency in Inducing Immune Dysfunction

Quetiapine versus Clozapine in Treating Psychiatric Patients with Severe COVID-19: A Netosis-Based Opinion

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

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