Type 17 Immune Response Facilitates Progression of Inflammation and Correlates with Cognition in Stable Schizophrenia

Abstract

Dysregulation of the type 17 immune pathway has already been considered in schizophrenia and we previously measured decreased sera values of interleukin (IL)-17 in early stages. We further explored the possible correlation of IL-17 systemic levels with proinflammatory cytokines and cognitive scores and additionally analyzed the percentage of IL-17 producing lymphocytes in peripheral blood of patients with stable schizophrenia. We included 27 patients diagnosed with schizophrenia (F20), after a three-month stable depot antipsychotic therapy (risperidone or paliperidone) and 18 healthy control subjects. Positive and Negative Syndrome Scale of Schizophrenia and the Montreal-Cognitive Assessment (MoCA) were conducted. Sera concentrations of IL-17, IL-6, tumor necrosis factor alpha (TNF-α) and soluble ST2 receptor (sST2) were measured. Flow cytometry and Natural Killer (NK) and T cell analyses were done in 10 patients and 10 healthy controls. Moderate positive correlation was established between IL-17 and TNF-α (r = 0.640; p = 0.001), IL-17 and IL-6 (r = 0.514; p = 0.006), IL-17 and sST2 (r = 0.394; p = 0.042). Furthermore, a positive correlation between the serum levels of IL-17 and MoCA scores was observed, especially with visuospatial and executive functioning, as well as language functioning and delayed recall (p < 0.05). Significantly higher percentage of IL-17 producing CD56+ NK cells was measured in peripheral blood of patients with schizophrenia in remission vs. healthy individuals (p = 0.001). The percentage of CD4+ T cells and CD4+ T cells that produce IL-17 was significantly increased in patients (p = 0.001). This study revealed the involvement of innate type 17 immune response in the progression of inflammation and this could be related to cognitive functioning in stable schizophrenia.

Interleukine-17 Modulates Neurogenesis and Behavior Following Exposure to Trauma in Mice

“…Furthermore, in a murine model for schizophrenia treated with mesenchymal stem cells, long term improved social behavior was achieved and was significantly correlated with increased hippocampal expression of IL-17 [48]. Indeed, it was recently reported that schizophrenia patients in remission following therapy had improved cognitive functions that were positively correlated with IL-17 serum levels [49]. Finally, a recent study demonstrated that local infusion of IL-17 to the somatosensory cortex of mice exhibiting impaired sociability due to maternal immune activation resulted in the reversal of social deficits [50].…”

Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment

“…Borovocanin et al reported decreased levels of IL-17 in schizophrenia patients ( 95 ), and found a significant decrease in Th17 cells. Recently, the percentage of IL-17-producing lymphocytes in peripheral blood of patients with stable schizophrenia and the possible correlation of IL-17 systemic levels with proinflammatory cytokines and cognitive scores was analyzed by Borovocanin et al ( 96 ).…”

Depression and Obesity in Patients With Psoriasis and Psoriatic Arthritis: Is IL-17-Mediated Immune Dysregulation the Connecting Link?

“…Immunome data demonstrate that paediatric patients with drug refractory epilepsy are characterized by an IL-17 inducing CD4 and CD8 cell subset profile, which likely contributes to epileptogenesis ( 39 ) while autism spectrum disorders are characterized by an imbalance between proinflammatory Th17 and suppressory T regulatory cells (Tregs) ( 40 ). Th17 cells are increased in patients with stable schizophrenia ( 41 ).…”