Parkinson’s disease (PD) is the second most common inflammatory neurodegenerative disorder after dementia, affecting 7–10 million people worldwide [1]. About 2–3% of elderly patients (aged ≥ 65 years) are affected by PD [2]. People with PD suffer motor symptoms such as bradykinesia, rigidity, resting tremor, and postural instability. In addition, patients often complain of ‘non-motor symptoms’ such as cognitive impairment, anxiety, depression, hypothermia, constipation, bowel and rapid eye movement sleep behavior disorder, and autonomic nervous system disorders [2,3].

PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, the appearance of Lewy bodies (intracellular inclusions of aggregated a-synuclein), and the presence of neuroinflammation [4,5,6,7]. Although the mechanism of neuron loss in PD is unclear, inflammation and the peripheral immune system play key roles [7,8,9]. Preclinical and epidemiological data suggest that chronic neuroinflammation induces neuronal dysfunction during the asymptomatic stage of PD [6,10]. The activation of resident microglia precedes dopamine neuron loss [11,12]. Activated microglia secrete several neurotoxic substances, such as chemokines and proinflammatory cytokines, which may cause blood–brain barrier (BBB) permeabilization and subsequent infiltration of peripheral leukocytes into the central nervous system (CNS) [11,12,13].

There is currently no cure for PD to prevent PD or delay its progression, mainly due to the still limited comprehension of the events ultimately leading to neurodegeneration. Available treatments for PD are only symptomatic, aimed at relieving the loss of brain dopaminergic neurons by using levodopa (the dopamine precursor), some dopaminergic agonists, and other indirect dopaminergic agents. Surgery, including deep brain stimulation, may be considered in advanced PD patients who fail to respond to levodopa [14].

CD4⁺ T lymphocytes play a pivotal role in orchestrating immune responses implicated not only in the pathogenesis of inflammatory diseases, but also in host defense. CD4⁺ T cells include proinflammatory cells such as T helper (Th) 1 and Th17, and anti-inflammatory cells such as Th2 and T regulatory cells (Tregs) [15,16]. Interestingly, both animal models of PD and clinical studies suggest that Th1 and Th17 can be detrimental to dopamine neurons, whereas Th2 and Tregs are neuroprotective [17,18]. Indeed, the number of circulating CD4⁺ T cells is reduced in patients with PD [19], but the relative proportions and functional profiles of subdivided cell populations are controversial. The decrease in CD4⁺ T cells seen in the peripheral blood of patients with PD is mainly due to decreases in Th2, Th17, and Tregs [20,21]. As a result, Th1 T cells, the absolute numbers of which are similar to healthy controls, increase in PD patients compared to other T cells, resulting in a Th1 bias. Consequently, the production of IFN-γ and TNF-α by Th1 cell lineages increases [21]. The results of studies on the serum levels of cytokines such as IFN-γ and TNF-α secreted by Th1 T cells, IL-8 and IL-10 secreted by Th2 T cells, and IL-17 secreted by Th17 in PD patients are not uniform [19,22,23,24,25,26,27]. In addition, the relationships between serum cytokine levels and motor and non-motor symptoms of PD are controversial [19,23,26,27].

Surgical stress and anesthesia induce inflammatory responses by disturbing the balance between pro- and anti-inflammatory cytokines [28], which may exacerbate the neuroinflammatory response in PD patients. The effects of inhalational anesthetics on the inflammatory response are controversial [29,30,31,32]. Meanwhile, Shan et al. [33] reported that sevoflurane worsened the prognosis of PD in a Drosophila model. There are few studies on the effect of the immune response on PD symptoms and prognosis after surgery and anesthesia [34,35,36,37].

2. Blood Inflammatory Biomarkers in PD Patients