Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children

Vk, Singh; Warren, Reed P.; Jd, Odell; Cole, P

doi:10.1016/s0090-1229(05)80015-7

Cited by 77 publications

(34 citation statements)

References 16 publications

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“…These results are in accordance with previous findings in autism reporting increased urinary levels of neopterin [11,12], elevated production of plasma IFN-· [13], increased serum T8 antigen and IL-2, another Th-1-like cytokine [14], and increased levels of IL-12 and IFN-Á [15]. At first sight, these results are not in agreement with previous reports showing signs of immunosuppression in autism (see Introduction).…”

Section: Discussionsupporting

confidence: 80%

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Activation of the Inflammatory Response System in Autism

Croonenberghs¹,

Bosmans²,

Deboutte³

et al. 2002

Neuropsychobiology

278

153

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Background/Aim: There is now some evidence that autism may be accompanied by abnormalities in the inflammatory response system (IRS). Products of the IRS, such as proinflammatory cytokines, may induce some of the behavioral symptoms of autism, such as social withdrawal, resistance to novelty and sleep disturbances. The main aim of the present study was to examine whether autism is accompanied by an activation of the IRS. Methods: We measured the production of interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1RA), interferon (IFN)-γ and tumor necrosis factor (TNF)-α by whole blood and the serum concentrations of IL-6, the IL-2 receptor (IL-2R) and IL-1RA. Results: This study showed a significantly increased production of IFN-γ and IL-1RA and a trend toward a significantly increased production of IL-6 and TNF-α by whole blood of autistic children. There were no significant differences in the serum concentrations of IL-6, IL-2R and IL-1RA between autistic and normal children. Conclusions: These results suggest that autism may be accompanied by an activation of the monocytic (increased IL-1RA) and Th-1-like (increased IFN-γ) arm of the IRS. It is hypothesized that increased production of proinflammatory cytokines could play a role in the pathophysiology of autism.

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Section: Discussionsupporting

confidence: 80%

“…The findings include increased urinary concentrations of neopterin [11,12], elevated plasma interferon (IFN)-· concentrations [13], increased levels of the T8 antigen and IL-2 [14] and increased concentrations of IL-12 and IFN-Á [15].…”

Section: Introductionmentioning

confidence: 99%

Activation of the Inflammatory Response System in Autism

Croonenberghs¹,

Bosmans²,

Deboutte³

et al. 2002

Neuropsychobiology

278

153

View full text Add to dashboard Cite

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“…50 Studies that assess cytokine levels in the periphery have often shown similar increases in proinflammatory cytokines, [51][52][53][54][55] as well as decreases in anti-inflammatory cytokines such as IL-10 24,52 and TGF␤. 56 However, not all studies have shown a consistent pattern of specific cytokines, and data so far collected suggest a complex pattern of immune activation that varies among different subgroups of individuals with ASD.…”

Section: Autoimmunity and Immune Dysfunction In Individuals With Asdmentioning

confidence: 99%

Immune Dysfunction in Autism: A Pathway to Treatment

2010

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Summary: Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.

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“…In an attempt to understand the overall activity of the immune system in subjects with autism, immune parameters in peripheral blood of subjects with autism spectrum disorders have been analyzed. These studies also indicated increased activation of innate immunity and Th1 lymphocytes (Ashwood et al 2011a;Ashwood et al 2011b;Croonenberghs et al 2002;Jyonouchi et al 2005;Jyonouchi et al 2002;Jyonouchi et al 2001;Singh 1996;Singh et al 1991;Sweeten et al 2004). In addition, elevated levels of immunoglobulins (Singer et al 2008;Singer et al 2006;Zimmerman et al 2007) and enhanced activity of natural killer cells (Enstrom et al 2009) in peripheral blood have been reported, as well as decreased numbers of regulatory T cells (Ashwood et al 2011b;Mostafa et al 2009) and reduced serum levels of TGF-beta (a cytokine typically released by regulatory T cells) (Ashwood et al 2008).…”

Section: Introductionmentioning

confidence: 87%

Risperidone-Related Improvement of Irritability in Children with Autism Is not Associated with Changes in Serum of Epidermal Growth Factor and Interleukin-13

Tobiásová

Lingen

Scahill

et al. 2011

Journal of Child and Adolescent Psychopharmacology

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Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-c (IFN-c), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n = 37) or risperidone (n = 40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n = 77) and healthy controls (recruited independently; n = 19). Serum levels of EGF were elevated in subjects with autism (median = 103 pg/mL, n = 75) in comparison to healthy controls (75 pg/mL, n = 19; p < 0.05), and levels of IL-13 were decreased in autism (median = 0.8 pg/ mL, n = 77) in comparison to controls (9.8 pg/mL, n = 19; p = 0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation.

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Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children

Cited by 77 publications

References 16 publications

Activation of the Inflammatory Response System in Autism

Activation of the Inflammatory Response System in Autism

Immune Dysfunction in Autism: A Pathway to Treatment

Risperidone-Related Improvement of Irritability in Children with Autism Is not Associated with Changes in Serum of Epidermal Growth Factor and Interleukin-13

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