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

Abstract

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.

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Moreover, blockade of AMPA receptors was able to reverse ketamine's effects on LPS-induced depressive-like behavior, indicating that the effects of ketamine were specific to its impact on glutamate signaling. Interestingly, a recent study demonstrated that serum concentrations of TNF, IL-1β, and IL-6 were significantly higher in treatmentresistant depressed patients who responded to ketamine versus nonresponders (Fan et al, 2015). Similarly, in a laboratory animal model of treatment-resistant depression, response to ketamine was also associated with increased measures of inflammation .…”

Altered Serum Tumor Necrosis Factor and Interleukin-1β in First-Episode Drug-Naive and Chronic Schizophrenia

“…They play an important role not only in the cell-cell communication but also in the function of the immune system in the central nervous system (CNS) (Müller et al, 2015 ). A number of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-1, and IL-6 have been found to involve in neuro-immune-endocrine communication and regulate neuronal activities in the mature CNS (Behrens et al, 2008 ; Fan et al, 2015 ; Schiavone and Trabace, 2017 ; Schiavone et al, 2017 ). Previous data have found altered levels of cytokines in the cerebrospinal fluid and the peripheral blood of patients with schizophrenia (Garver et al, 2003 ; Potvin et al, 2008 ; Rodrigues-Amorim et al, 2017 ), suggesting that cytokines may play an essential role in the etiology of schizophrenia (Fan et al, 2007 ; Song et al, 2009 ).…”

Low serum level of epidermal growth factor in chronic ketamine users

“…Several lines of evidence suggest that ketamine use influence cytokines, growth factors, and neurotrophic factors productions (Becker, Grecksch, Schwegler, & Roskoden, ; Chen, Chang, Lin, Ueng, & Chen, ; Fan, Luo, et al, ; Fan, Zhang, et al, ). Previously, we reported that serum levels of BDNF and nerve growth factor in chronic ketamine users were significantly lower than those in healthy subjects (Ke et al, ).…”

“…Several lines of evidence suggest that ketamine use influence cytokines, growth factors, and neurotrophic factors productions (Becker, Grecksch, Schwegler, & Roskoden, 2008;Chen, Chang, Lin, Ueng, & Chen, 2009;Fan, Luo, et al, 2015;.…”

“…The enrollment of study samples was as previously prescribed (Fan, Luo, et al, ; Fan, Zhang, et al, ; Ke et al, ). Briefly, ketamine users were recruited from two hospitals in Guangzhou, China.…”