Clean-up on IL-6 please

Cytokines, those little chemical messengers so intimately involved in processes like inflammation, are fast becoming a favourite topic of mine. I'm not an immunologist or cell biologist so can't readily claim to have an in-depth knowledge about their formation or action. Better perhaps to describe me as an amateur enthusiast but not necessarily to the Bedroom Biotech Inc. degree.

What I have come to understand is that not all cytokines are created equal. So alongside the different classes of cytokines, there are different functions to cytokines although with quite a bit of overlap in what they can do. In the case of inflammation for example, some cytokines have been termed pro-inflammatory and some anti-inflammatory. Anti-inflammatory cytokines like interleukin-10 (IL-10) for example, have cropped up in autism research as per previous posts like this one. Not one for sweeping generalisations, IL-10 has shown more than a passing interest to autism potentially reduced in some tissues in some cases.

Quite a bit more attention has been paid to some of the more pro-inflammatory cytokines in relation to autism spectrum conditions; interleukin-6 (IL-6) figuring quite heavily in the various reports. I say pro-inflammatory, but as with many things in life, it is not quite as black-and-white as that, given that these compounds are normally intricately tied into one and another in terms of signalling and activation.

Two recent reports caught my attention specifically with IL-6 and autism in mind. The first report by Garcia-Oscos and colleagues* has generated quite a bit of interest with regards to the suggestion that IL-6 might have a 'hyper-excitability' factor in terms of what it might specifically do to GABA-A receptors in the rat brain. To my Mr Men understanding, GABA is an inhibitory neurotransmitter. Reducing the number of, or altering the ability of certain receptors for GABA means that its inhibitory powers are going to be reduced. The suggestion therefore is that elevated levels of IL-6 over long periods leads to an imbalance in synaptic communication away from inhibition to excitatory as has been associated with conditions like epilepsy and autism.

The second paper by Wei and colleagues** also looked at IL-6 in the (mouse) brain suggesting a similarly perturbed balance between excitation and inhibitory synaptic transmissions when IL-6 was 'added', Said mice also displayed certain behaviours which are either core to an autism diagnosis (social interaction) or more peripheral (anxiety).

These coincidental accounts of IL-6 showing some influence to the delicate excitation/inhibition balance of synaptic signalling and potential link to autism is interesting. I have to admit that when I hear about cytokines, I don't automatically think about their effect on the brain given that many of the papers I come across are talking about links to other organs such as the gut***. Indeed, realising that IL-6 and various other cytokines can cross the blood-brain barrier (BBB) as well as as interacting to affect the sterling work undertaken by the BBB gives a new perspective on just what some of these critters might do when levels are perturbed.

* Garcia-Oscos F. et al. The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling. Biological Psychiatry. December 2011.
DOI: 10.1016/j.biopsych.2011.11.018

** Wei H. et al. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochmica et Biophysica acta. February 2012.

*** Arrieta MC. et al. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut. 2008; 58: 41-48
DOI: 10.1136/gut.2008.150888