Elevated Levels of Cerebrospinal Fluid and Plasma Interleukin-37 in Patients with Guillain-Barré Syndrome

Abstract

Aims. Interleukin-37 (IL-37) is an anti-inflammatory cytokine. This study aims to investigate the concentrations of plasma and cerebrospinal fluid (CSF) IL-37 in patients with Guillain-Barré Syndrome (GBS). Methods. The levels of plasma and CSF IL-37, IL-17A, IFN-γ, and TNF-α in 25 GBS patients and 20 healthy controls (HC) were determined by enzyme-linked immunoabsorbent assay and flow cytometric bead array assay, respectively. The values of clinical parameters in the patients were also measured. Results. The concentrations of plasma IL-37, IL-17A, IFN-γ, and TNF-α and CSF IL-37 and IL-17A in patients at the acute phase of GBS were significantly higher than those in the HC. The levels of plasma IL-37, IL-17A, IFN-γ, and TNF-α were positively correlated in those patients, and the levels of CSF IL-37 and IL-17A as well as the levels of plasma TNF-α were correlated positively with the GBS disability scale scores (GDSs) in those patients. Treatment with intravenous immunoglobulin significantly reduced the levels of plasma IL-37, IL-17A, IFN-γ, and TNF-α in the drug-responding patients. Conclusions. Our findings indicate higher levels of plasma and CSF IL-37 and IL-17A and other proinflammatory cytokines in patients with GBS.

IL-37 Is a Novel Proangiogenic Factor of Developmental and Pathological Angiogenesis

“…Indeed, as a secreted cytokine, IL-37 is upregulated in the serum of patients with systemic lupus erythematosus, Guillain-Barré syndrome, hepatitis B virus infection, and amyotrophic lateral sclerosis. 14,15,16,17 Here, we observed that IL-37 is expressed by ECs, suggesting angiogenic function of IL-37. Importantly, IL-37 expression and secretion is induced by hypoxia, a well-known proangiogenic conditions that stimulates angiogenesis and vascular alterations.…”

Expression of Early Growth Response Gene-2 and Regulated Cytokines Correlates with Recovery from Guillain–Barré Syndrome

“…The EGR2 or Krox-20 protein is a transcription factor involved in several processes such as immune response, early smooth musclelike cell differentiation, pathogenesis of fibrosis, and myelination in the peripheral nervous system with implications for the inherited peripheral neuropathies (5)(6)(7)(8)(9)(18)(19)(20). Furthermore, recent results have shown that EGR2 is induced by IL-6 and TGF-b and negatively regulates the expression of IL-17 but not IL-2 or IFN-g in effector T cells (20).…”

“…Furthermore, recent results have shown that EGR2 is induced by IL-6 and TGF-b and negatively regulates the expression of IL-17 but not IL-2 or IFN-g in effector T cells (20). The IL-6 and IL-17 are produced by activated Th17 cells, which are significantly increased in GBS patients (5)(6)(7)(8), and IL-17 and IL-22 levels have been implicated in the acute stage of GBS (7,8).…”

“…Although GBS is considered to be an autoimmune disease with the involvement of both cellular and humoral immune responses (2), little is known about the molecular mechanisms involved in the pathogenesis of GBS and its variants (2,(5)(6)(7)(8)(9). Strong evidence support a role for Th17 and IL-17 response in GBS (5)(6)(7)(8)(9), and that axonal subtypes of GBS, AMAN, and AMSAN are caused by Abs to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier (2).…”

“…Strong evidence support a role for Th17 and IL-17 response in GBS (5)(6)(7)(8)(9), and that axonal subtypes of GBS, AMAN, and AMSAN are caused by Abs to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier (2). About one-quarter of patients with GBS have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients (2,(10)(11)(12)(13)(14).…”