Meta-analysing cytokine involvement in autism

A fairly brief post today to draw your attention to the "systematic review and meta-analysis" paper by Masi and colleagues [1] on all-things cytokine in relation to autism. They concluded that there was "strengthening evidence of an abnormal cytokine profile in ASD [autism spectrum disorder] where inflammatory signals dominate". I should point out that other authors have reached similar conclusions in previous reviews [2] and here also [3].

"The herring does not fry here" @ Wikipedia 

In case you didn't know, cytokines are the chemical messengers of the immune system (see here) and perform various important tasks in relation to processes such as inflammation (see here). Autism research has a growing respect for the role of cytokines in quite a few cases of autism as per the growth in the amount of research literature available in this area (see here). I've covered quite a few papers focused on cytokines and autism on this blog (see here and see here for example) down the years.

The Masi paper is an important one because it gathered quite a bit of the peer-reviewed research literature mentioning cytokines and autism together and for want of better words, 'statistically spat' out the sum total of the findings from the various studies. A couple of old friends "were significantly higher in the participants with ASD" compared with control populations including interleukin 1-beta (IL-1β), IL-6, interferon-gamma (IFNγ) and monocyte chemotactic protein-1 (MCP-1) potentially indicative of a more pro-inflammatory state. A general reduction in the levels of more 'anti-inflammatory' molecules such as transforming growth factor-beta 1 (TGF-β1) [4] added to proceedings.

It's perhaps slightly unfair to say that these and other cytokines noted to be generally elevated in relation to autism are solely pro-inflammatory cytokines (i.e. inducing or maintaining inflammation) because that's not necessarily the way they always work. IL-6 for example, is now realised as being both a pro-inflammatory and anti-inflammatory molecule [5]. That being said, the growing recognition that inflammation and inflammatory processes may have some bearing on brain and behaviour (see here) ties in well with the Masi findings and where science perhaps needs to start looking with greater vigour if one is going to understand the interplay between immune function and psychiatry. As the authors note: "A better understanding of the inflammatory biology of ASD and possible associations with behavioral impairments and non-diagnostic features warrants further investigation and may have significant therapeutic implications". I can't argue with those sentiments, although as per the recent paper by Careaga and colleagues [6] how science goes about looking at that relationship is going to be important.

Oh, and on the topic of MCP-1, the paper by Zerbo and colleagues [7] observing elevations in the levels of this cytokine in newborn blood spots from those subsequently diagnosed with autism is indeed timely... (and again reiterates the potentially usefulness of those drops of blood which many children give in their earliest days welcomed into the big, wide world).

Music now. Daft Punk, and before Get Lucky, they were already Around the World.

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[1] Masi A. et al. Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Molecular Psychiatry. 2014. June 17.

[2] Goines PE. & Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicol Teratol. 2013 Mar-Apr;36:67-81.

[3] Onore C. et al. The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun. 2012 Mar;26(3):383-92.

[4] Qian L. et al. Potent anti-inflammatory and neuroprotective effects of TGF-beta1 are mediated through the inhibition of ERK and p47phox-Ser345 phosphorylation and translocation in microglia. J Immunol. 2008 Jul 1;181(1):660-8.

[5] Scheller J. et al. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2011; 1813: 878-888.

[6] Careaga M. et al. Inflammatory profiles in the BTBR mouse: How relevant are they to Autism Spectrum Disorders? Brain Behav Immun. 2014 Jun 14. pii: S0889-1591(14)00171-8.

[7] Zerbo O. et al. Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study. Journal of Neuroinflammation 2014, 11:113

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Masi, A., Quintana, D., Glozier, N., Lloyd, A., Hickie, I., & Guastella, A. (2014). Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis Molecular Psychiatry DOI: 10.1038/mp.2014.59