Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

Palladino, Ilaria; Salani, Francesca; Ciaramella, Antonio; Rubino, I. Alex; Caltagirone, Carlo; Fagioli, Sabrina; Spalletta, Gianfranco; Bossù, Paola

doi:10.1186/1742-2094-9-206

Cited by 29 publications

(13 citation statements)

References 25 publications

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“…Our results showed elevated levels of TNF-α, IL-6 in patients, providing further supporting evidence for the "macrophage Tlymphocyte" hypothesis. In addition, we found elevated serum levels of IL-18 in patients, which was agreed with previous studies in Japanese, Italian and Chinese schizophrenic patients (Reale et al, 2011;Palladino et al, 2012;Xiu et al, 2012). Since IL-18 is a member of the IL-1 family of proinflammatory cytokines and plays an important role in the activation of Th1 cells, our present result of increased IL-18 also support the activated macrophage theory.…”

supporting

confidence: 95%

“…Schizophrenia patients showed significant altered levels of blood interleukin-1 RA (IL-1RA), sIL-2R, IL-6 and tumor necrosis factoralpha (TNF-α) (Potvin et al, 2008;Song et al, 2013). Several recent studies have shown that IL-18 levels, a member of the IL-1 family of proinflammatory cytokines, are remarkably higher in schizophrenic patients than in controls and are correlated with the psychopathology of schizophrenia (Reale et al, 2011;Palladino et al, 2012;Xiu et al, 2012). Howerver,there were inconsistent of the findings about serum levels of cytokines.…”

mentioning

confidence: 98%

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Elevated serum levels of TNF-α, IL-6 and IL-18 in chronic schizophrenic patients

Luo

Zhang

et al. 2014

Schizophrenia Research

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supporting

confidence: 95%

mentioning

confidence: 98%

Elevated serum levels of TNF-α, IL-6 and IL-18 in chronic schizophrenic patients

Luo

Zhang

et al. 2014

Schizophrenia Research

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“…Dysregulation of the IL-18/IL-18BP equilibrium characterizes several inflammatory diseases, including schizophrenia, where IL-18BP is increased [48]. In contrast, the present study describes that the IL-18/IL-18BP balance was preserved among the studied groups, which is not surprising in healthy subjects.…”

Section: Discussioncontrasting

confidence: 53%

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study

Sacchinelli¹,

Piras²,

Orfei³

et al. 2018

Neuroimmunomodulation

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Objective: Interaction between the nervous and immune systems may influence emotions, ultimately affecting human health. Cytokines may play a role in developing emotional dysregulation as in alexithymia, a personality construct characterized by the subclinical inability to identify and describe emotions, often associated with several psychiatric and psychosomatic disorders. The proinflammatory cytokine IL-18, with a recognized role in brain functions, may influence serotonin metabolism and appears to be associated with alexithymia. Healthy individuals carrying the long allele (L) of the serotonin transporter gene polymorphic region (5-HTTLPR), and thus having lower concentrations of serotonin in the synaptic cleft, show a greater tendency toward alexithymia, with some gender differences. To explore a potential physiological interaction between IL-18, serotonin neurotransmission, and alexithymia, we investigated whether IL-18 serum levels and 5-HTTLPR are linked to alexithymic traits in healthy subjects. Methods: We measured IL-18 serum levels in 115 Italian-Caucasian healthy subjects genotyped for 5-HTTLPR allele variants, divided by gender and assessed for alexithymia scores using the 20-item Toronto Alexithymia Scale. Results: IL-18 levels are significantly more elevated in individuals with the LL genotype (n = 25) than in carriers of the short allele (n = 90, p = 0.0073). Specifically, in LL males (n = 11), i.e., the group with the most relevant increase in IL-18, cytokine values positively correlated with difficulty identifying feelings, which is a component of alexithymia (r = 0.634, p = 0.036). Conclusions: These results indicate a possible novel interaction between IL-18 and the serotoninergic system to mediate emotional unawareness, suggesting putative biological predictors of emotional dysregulation, which in turn can act as a risk factor for a variety of medical conditions in susceptible subjects.

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“…Therefore, IL-18 appears to be a communication signal between the nervous and immune systems, mediating neuroinflammatory and neurodegenerative processes as well as influencing homeostasis and behavior (Alboni et al, 2010). Previous studies in Japanese, Italian and Chinese schizophrenic patients have shown that Il-18 level was remarkably higher in schizophrenia patients than in controls (Tanaka et al, 2000; Reale et al, 2011; Xiu et al, 2012; Palladino et al, 2012; Luo et al, 2014) indicating alterations of IL-18 may be involved in pathophysiology of schizophrenia. To date, there have been no reports to study the role of IL-18 in ketamine animal or human model of schizophrenia.…”

Section: Discussionmentioning

confidence: 89%

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

Fan

Luo

Zhang

et al. 2015

Schizophrenia Research

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Objective Exposing to NMDAR receptor antagonists, such as ketamine, produces schizophrenia-like symptoms in humans and deteriorates symptoms in schizophrenia patients. Meanwhile, schizophrenia is associated with alterations of cytokines in the immune system. This study aims to examine the serum TNF-α, IL-6 and IL-18 levels in chronic human ketamine users as compared to healthy subjects. The correlations between the serum cytokines levels with the demographic, ketamine use characteristics and psychiatric symptoms were also assessed. Methods 155 subjects who fulfilled the criteria of ketamine dependence and 80 healthy control subjects were recruited. Serum TNF-α, IL-6 and IL-18 levels were measured using an enzyme-linked immunosorbent assay (ELISA). The psychiatric symptoms of the ketamine abusers were assessed using the Positive and Negative Syndrome Scale (PANSS). Results Serum IL-6 and IL-18 levels were significantly higher, while serum TNF-α level was significantly lower among ketamine users than among healthy controls (p < 0.05). Serum TNF-α levels showed a significant negative association with PANSS total score (r = −0.210, p < 0.01) and negative subscore (r = −0.300, p < 0.01). No significant association was found between PANSS score and serum levels of IL-6 and IL-18. Conclusions Serum levels of TNF-α, IL-6 and IL-18 were altered in chronic ketamine abusers which may play a role in schizophrenia-like symptoms in chronic ketamine abusers.

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Elevated levels of circulating IL-18BP and perturbed regulation of IL-18 in schizophrenia

Cited by 29 publications

References 25 publications

Elevated serum levels of TNF-α, IL-6 and IL-18 in chronic schizophrenic patients

Elevated serum levels of TNF-α, IL-6 and IL-18 in chronic schizophrenic patients

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

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