Abstract

BackgroundIn neuromyelitis optica (NMO), one of the underlying pathogenic mechanisms is the formation of antigen-antibody complexes which can trigger an inflammatory response by inducing the infiltration of neutrophils in lesions. Epithelial neutrophil-activating peptide 78 (ENA 78), known as Chemokine (C-X-C motif) ligand 5 (CXCL5), belongs to the ELR-CXCL family. It recruits and activates neutrophils. The aim of this study was to evaluate ENA 78, IL-1β and TNF-α plasma levels in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients.MethodsENA 78, IL-1β and TNF-α plasma levels were detected in 20 healthy controls (HC), 25 MS and 25 NMO patients using MILLIPLEX® map Human High Sensitivity Cytokine/Chemokine Panels.ResultsPlasma levels of ENA 78 were significantly higher in NMO patients than in HC (P < 0.001) and MS patients (P < 0.05). The NMO patients showed higher plasma levels of IL-1β compared with HC (P < 0.01). Further, increased plasma levels of TNF-α were found in the MS (P < 0.05) and NMO patients (P < 0.001). In addition, NMO patients had higher Expanded Disability Status Scale (EDSS) scores compared with MS patients (P < 0.05). EDSS scores were correlated with plasma levels of ENA 78 in NMO patients (P < 0.05). There were no significant correlations between EDSS scores and plasma levels of ENA 78 in MS patients (P > 0.05).ConclusionsThe overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α during the remission of NMO activates ENA 78, which in turn leads to neutrophil infiltration in lesions. ENA 78 plasma levels were correlated with EDSS scores in NMO patients. Elevated secretion of ENA 78 may be a critical step in neutrophil recruitment during the remission of NMO.

Highlights

  • In neuromyelitis optica (NMO), one of the underlying pathogenic mechanisms is the formation of antigen-antibody complexes which can trigger an inflammatory response by inducing the infiltration of neutrophils in lesions

  • Increased plasma epithelial neutrophilactivating peptide (ENA) 78, interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) levels in NMO patients Epithelial neutrophil-activating peptide 78 (ENA 78) expression was higher in NMO plasma than in healthy controls (HC) (P < 0.001) and multiple sclerosis (MS) (P < 0.05) (Fig. 1a)

  • In summary, the overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α during remission of NMO might result in activation of ENA 78

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Summary

Introduction

In neuromyelitis optica (NMO), one of the underlying pathogenic mechanisms is the formation of antigen-antibody complexes which can trigger an inflammatory response by inducing the infiltration of neutrophils in lesions. Epithelial neutrophil-activating peptide 78 (ENA 78), known as Chemokine (C-X-C motif) ligand 5 (CXCL5), belongs to the ELR-CXCL family. The aim of this study was to evaluate ENA 78, IL-1β and TNF-α plasma levels in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. A significant feature distinguishing NMO from MS is the relatively higher number of neutrophils, eosinophils, macrophages and fewer T cells in the lesions [2, 8, 9]. Abnormal neutrophil aggregation in the lesions and increased AQP4-IgG are the notable features distinguishing NMO from MS [8, 10].

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