Abstract
Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder in early childhood characterized by impairment in communication and behavior. Recent research is focused on the immune dysregulation as a potential pathomechanism leading to ASD. Thus, we addressed the hypothesis that inflammatory activity might be enhanced in children suffering from ASD. We examined 15 children with ASD (13 boys/2 girls, mean age of 9.3 ± 0.7 years) and 20 age/gender-matched healthy subjects as a control group. All children were medication free and in good health. Hematological parameters in venous blood and plasma levels of pro-inflammatory cytokines - tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 8 (IL-8) – were assessed in each subject using human ultra-sensitive ELISA kits. In addition, TBARS as a marker of oxidative stress was evaluated. We found that the level of IL-8 was significantly increased in the ASD children, whereas the other markers remained unappreciably changed compared to controls (p = 0.003). In conclusion, the study demonstrates a discrete immune dysfunction in ASD of pro-inflammatory character.
Keywords
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, Washington, DC, pp 50–59
Ashwood P, Wakefield AJ (2006) Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol 173:126–134
Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA, Ozonoff S, Pessah IN, Van de Water J (2008) Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol 204:149–153
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen RL, Pessah IN, Van de Water J (2011a) Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25:40–45
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J (2011b) Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 23:196–199
Bernardino L, Agasse F, Silva B, Ferreira R, Grade S, Malva JO (2008) Tumor necrosis factor-alpha modulates survival, proliferation, and neuronal differentiation in neonatal subventricular zone cell cultures. Stem Cells 26:2361–2371
Cacci E, Claasen JH, Kokaia Z (2005) Microglia-derived tumor necrosis factor-alpha exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res 80:789–797
Cacci E, Ajmone-Cat MA, Anelli T, Biagioni S, Minghetti L (2008) In vitro neuronal and glial differentiation from embryonic or adult neural precursor cells are differently affected by chronic or acute activation of microglia. Glia 56:412–425
Corbett BA, Kantor AB, Schulman H, Walker WL, Lit L, Ashwood P, Rocke DM, Sharp FR (2007) A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins. Mol Psychiatry 12:292–306
Depino AM (2013) Peripheral and central inflammation in autism spectrum disorders. Mol Cell Neurosci 53:69–76
Derecki NC, Cardani AN, Yang CH, Quinnies KM, Crihfield A, Lynch KR, Kipnis J (2010) Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 207:1067–1080
Deverman BE, Patterson PH (2009) Cytokines and CNS development. Neuron 64:61–78
Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen RL, Pessah IN, Hertz-Picciotto I, Van de Water JA, Sharp FR, Ashwood P (2009) Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun 23:124–133
Enstrom AM, Onore CE, Van de Water JA, Ashwood P (2010) Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain Behav Immun 24:64–71
Gilmore JH, Jarskog LF, Vadlamudi S (2005) Maternal poly I:C exposure during pregnancy regulates TNFα, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat. J Neuroimmunol 159:106–112
Goines PE, Ashwood P (2013) Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicol Teratol 36:67–81
Noriega DB, Savelkoul HF (2014) Immune dysregulation in autism spectrum disorder. Eur J Pediatr 173:33–43
Onore C, Careaga M, Ashwood P (2012) The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun 26:383–392
Porges SW, Macellaio M, Stanfill SD, McCue K, Lewis GF, Harden ER, Handelman M, Denver J, Bazhenova OV, Heilman KJ (2013) Respiratory sinus arrhythmia and auditory processing in autism: modifiable deficits of an integrated social engagement system? Int J Psychophysiol 88:261–270
Schneider H, Pitossi F, Balschun D, Wagner A, del Rey A, Besedovsky HO (1998) A neuromodulatory role of interleukin-1beta in the hippocampus. Proc Natl Acad Sci U S A 95:7778–7783
Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Mori N (2011) Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One 6:e20470
Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW (1994) Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 83:113–118
Tracey KJ (2002) The inflammatory reflex. Nature 420:853–859
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67–81
Williams CL, Teeling JL, Perry VH, Fleming TP (2011) Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring. BMC Biol 9:49
Acknowledgments
This work was supported by National Research Grant VEGA 1/0087/14, APVV-0254-11 and BioMed Martin (ITMS: 26220220187). The project was co-financed by the European Union.
Conflicts of Interest
The authors declare no conflicts of interest in relation to this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Tonhajzerova, I. et al. (2015). Inflammatory Activity in Autism Spectrum Disorder. In: Pokorski, M. (eds) Respiratory Health. Advances in Experimental Medicine and Biology(), vol 861. Springer, Cham. https://doi.org/10.1007/5584_2015_145
Download citation
DOI: https://doi.org/10.1007/5584_2015_145
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-18792-1
Online ISBN: 978-3-319-18793-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)