Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6.

I Tsilioni,T C Theoharides,A Taliou,K Francis

doi:10.1038/tp.2015.142

Abstract

Autism spectrum disorders (ASDs) have been associated with brain inflammation as indicated by microglia activation, as well as brain expression and increased plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF). Here we report that serum levels of IL-6 and TNF were elevated (61.95±94.76 pg ml−1 and 313.8±444.3 pg ml−1, respectively) in the same cohort of patients with elevated serum levels of corticotropin-releasing hormone (CRH) and neurotensin (NT), while IL-9, IL-31 and IL-33 were not different from controls. The elevated CRH and NT levels did not change after treatment with a luteolin-containing dietary formulation. However, the mean serum IL-6 and TNF levels decreased significantly (P=0.036 and P=0.015, respectively) at the end of the treatment period (26 weeks) as compared with levels at the beginning; these decreases were strongly associated with children whose behavior improved the most after luteolin formulation treatment. Our results indicate that there are distinct subgroups of children within the ASDs that may be identifiable through serum levels of IL-6 and TNF and that these cytokines may constitute distinct prognostic markers for at least the beneficial effect of luteolin formulation.

Highlights

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interactions and communication, as well as stereotypic behaviors.[1,2,3,4] The prevalence of autism spectrum disorder (ASD) is estimated to be 1 in 68 children.[5]
Our study shows two clusters of ASD children with low and high serum IL-6 and tumor necrosis factor (TNF) levels, indicating two subgroups
ASDs in which the elevated serum IL-6 and TNF levels decreased at the end of the treatment period with a luteolin formulation, were the ones whose behavior improved the most

Summary

INTRODUCTION

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interactions and communication, as well as stereotypic behaviors.[1,2,3,4] The prevalence of ASDs is estimated to be 1 in 68 children.[5]. Luteolin inhibited IL-6 release from activated microglia[40] and reduced maternal IL-6-induced autism-like behavioral deficits related to social interactions in mice.[41] Luteolin inhibits MC-dependent stimulation of activated T cells,[42] and is neuroprotective.[43] It inhibits stimulation of astrocytes,[44] as well as microglial activation and proliferation,[45,46,47] protects against thimerosal-induced inflammatory mediator release from MCs 48 and methylmercury-induced mouse brain mitochondrial damage.[49] One open-label clinical study showed that a luteolincontaining dietary formulation significantly improved sociability in children with ASDs.[50]. The results are presented as scattergrams with symbols representing individual

MATERIALS AND METHODS

DISCUSSION

Findings

CONFLICT OF INTEREST