Altered serum levels of IL-36 cytokines (IL-36α, IL-36β, IL-36γ, and IL-36Ra) and their potential roles in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute autoimmune neurological disorder mainly involving the peripheral nerves. Currently, various cytokines have been shown to be involved in the pathogenesis of GBS. Because of their similar biological structures, interleukin (IL)-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist (Ra) were all renamed and collectively called IL-36 cytokines. The roles of IL-36 cytokines in GBS currently remain unclear. Forty-two patients with GBS and 32 healthy volunteers were included in our study. Serum IL-36α, β, γ, and interleukin-36 receptor antagonist (IL-36Ra) levels of patients with GBS in the acute and remission phases and healthy volunteers were measured by enzyme-linked immunosorbent assay (ELISA). In addition, we examined the serum levels of other inflammatory factors that have been shown to be involved in GBS pathogenesis, represented by IL-17 and tumor necrosis factor-α (TNF-α). Furthermore, the correlations between the serum levels of IL-36 cytokines and different clinical data or the serum levels of other inflammatory factors in GBS patients were analyzed. Significantly higher serum IL-36α and IL-36γ levels were measured in the acute phase than in the remission phase and in healthy control (HC) subjects (P < .05), while lower serum IL-36Ra levels were measured in the acute phase than in the remission phase and in HC subjects (P < .05). Serum IL-36α and IL-36γ levels were positively correlated with GBS disability scale scores (GDSs), while serum IL-36Ra levels were negatively correlated with GDSs. Correlation analyses among inflammatory factors showed that serum IL-36α and IL-36γ levels in GBS patients were positively correlated with serum IL-17 and TNF-α levels, while serum IL-36Ra levels were negatively correlated with the levels of these 2 inflammatory factors. Similar results were observed in cerebrospinal fluid (CSF), IL-36α and IL-36γ levels in CSF were positively correlated with GDSs, while IL-36Ra levels in CSF were negatively correlated with GDSs. Additionally, the serum and CSF levels of IL-36α and IL-36γ in the axonal subtype of GBS patients were higher than those in the demyelination subtype. Based on our findings, IL-36 cytokines may be involved in the pathogenesis of GBS and some of these cytokines may help predict the disease severity and other clinical characteristics of GBS.