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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Psychiatry | doi: 10.3389/fpsyt.2019.00152

Anti-inflammatory effect of ghrelin in lymphoblastoid cell lines from children with autism spectrum disorder

 Yasunori Yamashita1,  Manabu Makinodan2*,  Michihiro Toritsuka1,  Takahira Yamauchi1, Daisuke Ikawa1, Sohei Kimoto1,  Takashi Komori1, Ryohei Takada1,  Yoshinori Kayashima1, Kaori Hamano-Iwasa1, Masatsugu Tsujii3, Hideo Matsuzaki4 and Toshifumi Kishimoto1
  • 1Department of Psychiatry, Nara Medical University, Japan
  • 2Nara Medical University, Japan
  • 3Graduate School of Sociology, Chukyo University, Japan
  • 4Research Center for Child Mental Development, University of Fukui, Japan

The gut hormone ghrelin has been implicated in a variety of functional roles in the central nervous system through the brain-gut axis, one of which is an anti-inflammatory effect. An aberrant brain-gut axis producing immune dysfunction has been implicated in the pathobiology of autism spectrum disorder (ASD), and elevated expression of inflammatory markers has been shown in blood and brain tissue from subjects with ASD. We hypothesized that ghrelin may mitigate this effect,. Lymphoblastoid cell lines from typically developed children (TD-C) (N = 20) and children with ASD (ASD-C) (N = 20) were cultured with PBS or human ghrelin (0.01 μM) for 24 hours, and mRNA expression levels of the inflammation-related molecules interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B (NF-κB) were measured to examine the effects of ghrelin as an anti-inflammatory agent. Expression levels of TNF-α and NF-κB mRNA, but not IL-1β or IL-6, were significantly elevated in ASD-C compared to TD-C. Ghrelin showed a tendency to reduce the expression of TNF-α and NF-κB, but this was not statistically significant. Considering the heterogenous pathobiology of ASD, we examined the effects of ghrelin on TD-C and ASD-C with expression levels of TNF-α and NF-κB in the highest and lowest quartiles. We found that ghrelin markedly reduced mRNA expression of TNF-α and NF-κB s in ASD-C with highest-quartile expression, but there were no effects in ASD-C with lowest-quartile expression, TD-C with highest quartile expression, or TD-C with lowest quartile expression. Together, these findings suggest that ghrelin has potential as a novel therapeutic agent for ASD with inflammation and/or immune dysfunction.

Keywords: Ghrelin, autism, Lymphoblastoid cell line, cytokine, Immune System

Received: 30 Aug 2018; Accepted: 28 Feb 2019.

Edited by:

Jean Marc Guile, University of Picardie Jules Verne, France

Reviewed by:

Munis Dundar, Erciyes University, Turkey
Ben Nephew, Worcester Polytechnic Institute, United States  

Copyright: © 2019 Yamashita, Makinodan, Toritsuka, Yamauchi, Ikawa, Kimoto, Komori, Takada, Kayashima, Hamano-Iwasa, Tsujii, Matsuzaki and Kishimoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Manabu Makinodan, Nara Medical University, Kashihara, Japan, mmm@naramed-u.ac.jp