Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis.

Paola Italiani,Paola Bossù,Paola Migliorini,Cecilia Carlesi,Diana Boraschi,Paola Giungato,Ilaria Puxeddu,Gabriele Siciliano,Barbara Borroni

doi:10.1186/1742-2094-11-94

Abstract

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to the death of affected individuals within years. The involvement of inflammation in the pathogenesis of neurodegenerative diseases, including ALS, is increasingly recognized but still not well understood. The aim of this study is to evaluate the levels of inflammation-related IL-1 family cytokines (IL-1β, IL-18, IL-33, IL-37) and their endogenous inhibitors (IL-1Ra, sIL-1R2, IL-18BP, sIL-1R4) in patients with sporadic ALS (sALS),MethodsSera were collected from 144 patients (125 patients were characterized by disease form, duration, and disability, using the revised ALS functional rating scale (ALSFRS-R) and from 40 matched controls. Cerebrospinal fluid (CSF) was collected from 54 patients with sALS and 65 patients with other non-infectious non-oncogenic diseases as controls. Cytokines and inhibitors were measured by commercial ELISA.ResultsAmong the IL-1 family cytokines tested total IL-18, its endogenous inhibitor IL-18BP, and the active form of the cytokine (free IL-18) were significantly higher in the sALS sera than in controls. No correlation between these soluble mediators and different clinical forms of sALS or the clinical setting of the disease was found. IL-18BP was the only mediator detectable in the CSF of patients.ConclusionsAmong the IL-1 family cytokines, only IL-18 correlates with this disease and may therefore have a pathological role in sALS. The increase of total IL-18 suggests the activation of IL-18-cleaving inflammasome. Whether IL-18 upregulation in circulation of sALS patients is a consequence of inflammation or one of the causes of the pathology still needs to be addressed.

Highlights

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to the death of affected individuals within years
At variance with IL-1, IL-18 was measurable in sera and its levels were significantly increased in Sporadic ALS (sALS) compared to normal healthy subjects (NHS) (P
The data collected in the current study shows that, among the cytokines of the IL-1 family tested, only IL-18 and IL-18 binding protein (IL-18BP) are increased in the serum of sALS patients

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to the death of affected individuals within years. The aim of this study is to evaluate the levels of inflammation-related IL-1 family cytokines (IL-1β, IL-18, IL-33, IL-37) and their endogenous inhibitors (IL-1Ra, sIL-1R2, IL-18BP, sIL-1R4) in patients with sporadic ALS (sALS), Methods: Sera were collected from 144 patients (125 patients were characterized by disease form, duration, and disability, using the revised ALS functional rating scale (ALSFRS-R) and from 40 matched controls. An involvement of IL-1 family cytokines in the pathology of ALS has been suggested by the finding of activated caspase-1 and increased IL-1β both in ALS mouse models and in patients [11,12,13]. The IL-1 family includes eight cytokines with inflammatory or anti-inflammatory activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-37), and three receptor antagonists (IL-1Ra, IL-36Ra, IL-38) [14,15]. IL-1R2 functions as a decoy receptor for IL-1β, capturing the cytokine and preventing its interaction with IL-1R1 [16,19]

Objectives

Methods

Results

Discussion

Conclusion