Various studies have demonstrated that the pathogenesis of PD involves neuroinflammation, which is affected by both innate and adaptive immunity, and the levels of proinflammatory cytokines are elevated in PD patients [5, 13–15]. Th17 cells are among the most important lymphocytes involved in degeneration of dopaminergic neurons in PD . Th17 cells secrete the proinflammatory cytokine IL-17, which is commonly associated with allergic responses. IL-17 promotes the secretion of other cytokines, such as IL-1β and TNF-α, and plays a pivotal role in the early stages of inflammation. These cytokines bind to receptors on dopaminergic neurons, resulting in apoptosis [4, 6, 16].
To the best of our knowledge, this is the first study to investigate the effects of anesthetic method on inflammatory response in patients with PD. IL-17 at 24 h after surgery tended to increase under inhalational anesthesia, while it was maintained at the preoperative baseline level under TIVA. IL-1β and TNF-α also tended to increase at 24 h after surgery under inhalational anesthesia, but the effect was not significant. These results suggest that TIVA has advantages with regard to inhibition of neuroinflammation after surgery in PD patients despite its lack of statistical significance. Surgical stress and anesthesia induce inflammatory responses by disturbing the balance between pro- and antiinflammatory cytokines , which may result in aggravation of the neuroinflammatory response in PD patients. Previous studies have indicated that TIVA has superior effects in inhibiting inflammatory responses to inhalational anesthetics [9, 17–19]. Shan et al.  reported that the inhalational anesthetic sevoflurane has a negative effect and aggravates the prognosis of PD in a Drosophila model. We attributed the lack of statistical significance in this study to the relatively short duration of surgery and the follow-up of only 24 h after surgery may not have been sufficient to reveal cytokine changes. A decline of immunity due to surgery and anesthesia occurs from roughly 2 h after induction of anesthesia, and the peak of immunosuppression occurs 3 days after surgery . We obtained blood samples 2 h after induction of anesthesia when changes in the immune responses had just begun and 24 h after surgery when changes had not yet reached their peak.
The baseline IL-17 level in this study was about 700 pg/mL. Sommer et al.  reported that IL-17 levels in PD patients were about 350 pg/mL, while they were below 50 pg/mL in controls. Resting tremor, rigidity, bradykinesia, and impairment of balance are characteristic motor symptoms of PD. Shan et al.  reported that impairment of locomotor abilities is aggravated with exposure to sevoflurane in a Drosophila PD model. Tuon et al.  reported that IL-17 levels decrease after physical training in an experimental mouse model of PD. Williams-Gray et al.  showed that serum levels of cytokines, such as IL-1β, TNF-α, and IL-10, are higher in PD patients than in age-matched non-PD controls; higher TNF-α levels are associated with faster rates of motor decline and higher IL-1β levels are associated with a faster rate of cognitive decline. These studies suggest that IL-17 and TNF-α are closely related to the motor symptoms of PD. Our cohort consisted of patients who had been diagnosed with PD for about 10 years and required cerebral stimulator implantation to manage motor symptoms that were not controlled by medications. These observations suggest that serum levels of IL-17 increase with the progression of PD. That is, neuroinflammation induced by Th-17 cells causing neuronal cell apoptosis may be an important factor in the progression of PD symptoms. Thus, serum IL-17 may be used as a biomarker for PD progression.
However, our results did not reach statistical significance. As no similar clinical studies have been reported in the literature, we used the results from an experimental animal study for sample size calculation . In that study, the authors analyzed the levels of IL-17 in the brain tissue of a mouse model of PD 24 h after the intervention. However, the baseline IL-17 level is different between mice and humans. Nevertheless, we believe that this study was worthwhile as a pilot study in that it determined the baseline serum level of IL-17 for use in future clinical studies on PD. In addition, we did not examine the motor symptoms before and after surgery in relation with cytokine changes. We selected PD patients undergoing brain stimulator implantation, and it would have been difficult to evaluate the motor symptoms before surgery due to the severity of PD and after surgery due to the stimulation. We intend to compare changes in short- and long-term motor symptoms in relation to cytokine changes in a future study.
In conclusion, TIVA may be useful for inhibiting neuroinflammation by inhibiting the increase in serum levels of IL-17 24 h after implantation surgery. Serum IL-17 level may be used as a biomarker for PD progression since it was much higher in PD patients with severe motor symptoms. Further clinical trials to investigate the relationships between changes in cytokine levels and motor symptoms are needed.