Elsevier

Cytokine

Volume 108, August 2018, Pages 120-126
Cytokine

Cytokine profile in autistic patients

https://doi.org/10.1016/j.cyto.2018.03.034Get rights and content

Abstract

The etiology of Autism Spectrum Disorders (ASDs) as severe neurodevelopmental ailments is not known. However, several evidences point to dysregulation of immune system as an underlying cause of ASD. In the present study we evaluated the mRNA expression levels of TNF-α, TGF-β, IFN-γ, CXCL8, IL-1β, IL-2, 1L-4, IL-6, IL-17 in whole blood samples of 30 ASD patients and 41 age and sex-matched healthy subjects with means of real-time PCR. TNF-α, IL-6 and IL-17 have been shown to be significantly up-regulated in ASD patients compared with healthy subjects (P < 0.0001, P = 0.001 and P < 0.0001 respectively). IL-2 has been shown to be significantly down-regulated in total ASD patients (P < 0.0001). No significant difference has been found in expression levels of other cytokines between patients and healthy subjects. The present study provides further evidences for dysregulation of immune response in ASD patients.

Introduction

Autism Spectrum Disorders (ASDs) as neurodevelopmental disorders are outlined by inadequacy of social communication and interaction, and the existence of limited, monotonous patterns in behavior, passion, or motions [1]. Although the exact underlying mechanism is not clear, evidences have supported a role for dysregulation of immune system [2]. Numerous studies have demonstrated changes in the cytokine levels in the blood, brain, and cerebrospinal fluid (CSF) of ASD patients compared with healthy subjects [3]. Furthermore, alteration in the expression of immune factors has been associated with the severity of ASD complications such as defects in social interactions or monotonous behaviors [4]. Abnormal T helper (Th) cell responses are implicated in the ASD development as well. Th cells are divided to distinct classes based on their functions and cytokine-secretion phenotypes. Th1 cells produce interleukin (IL-2), interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Th2 cells produce IL-4, -5, -10 and -13 and participate in the development of auto-immune disorders. Th17 cells secrete IL-17, IL-17F, IL-6, IL-22 and TNF-α and contribute in tissue inflammation. On the other hand, regulatory T (Treg) cells secrete IL-10 and transforming growth factor (TGF)-β, which modify Th functions and contribute in tolerance induction [5]. In addition to these cytokines, CXCL8 (IL-8) is a small protein which is expressed in polymorphonuclear leukocytes, as well as epithelial, endothelial, fibroblasts and neurons. This chemokine participates in defense against pathogens as well as some disease-associated processes such as tissue injury, fibrosis and angiogenesis [6].

In the present study we aimed at mRNA expression analysis of pro-inflammatory (IL-1β, IL-6 and TNF-α), Th1 (IL-2 and IFN-γ), Th2 (IL-4), Th17 (IL-17) cytokines as well as CXCL8 chemokine and TGF-β (an indicator of Treg cell activity) in whole blood cells of ASD patients as compared with healthy subjects.

Section snippets

Patients and control group

This case–control study consisted of 30 Iranian ASD patients (mean age of 6 ± 1.4) and 41 age, gender, and ethnic-matched healthy controls (mean age of 6 ± 1.4). ASD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition criteria (1). The exclusion criteria were the existence of any other neurological, metabolic or auto-immune disorders. None of the ASD patients had a comorbid disorder such as attention deficit hyperactive disorder. Controls were

General data

The patient group included 30 ASD patients (Male/Female = 19/11) with age (mean ± standard deviation (SD)) of 6 ± 1.4. The control group consisted 41 healthy subjects (Male/Female = 30/11) with age (mean ± SD) of 6 ± 1.74.

Relative mRNA expression of CXCL8 in patients compared with healthy subjects

No significant difference has been found in CXCL8 mRNA expression between patients and healthy subjects or within age and sex subgroups (Table 2). After application of ANCOVA for adjusting the effects of sex and age, there was no statistically significant difference in CXCL8

Discussion

In the present study we demonstrated significant higher expression of TNF-α, IL-17 and IL-6 while lower expression of IL-2 in whole blood samples of ASD patients compared with healthy subjects. We also demonstrated significant correlations between the levels of cytokines which implies the presence of an interactive network between them. In addition, compared with the previous studies which determined the plasma concentration of cytokines using ELISA kits, we assessed mRNA transcripts levels of

Acknowledgement

The present study was supported by a grant number 960129389 from Hamadan University of Medical Sciences.

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The first two authors contributed equally.

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