Immune system

The molecular patters of infection, damage or danger to our bodies, act like barcodes to alert our immune system that something is up. It responds with inflammation, one of the fundamental ways by which we defend and repair ourselves. Inflammation is driven by our white blood cells and their communication molecules, the cytokines. It’s a form of oxidative stress and our best defence against infection, but one that unfortunately inflicts unintended collateral damage to our tissues as part & parcel of doing its job. Which is why by design, it is only ever meant to be an acute, short term assault, and a proxy to a pro-resolving return to the status quo. When triggered incongruously or inappropriately regulated, unruly 'silent' inflammation becomes quietly problematic, no longer acute, it sits below the threshold of perception, a core feature of an underlying immune dysregulation.

We see this 'silent' inflammation unleashed in many circumstances and is now considered a catalyst for an increasing number of non-infectious, chronic degenerative diseases (autoimmunity, allergy, metabolic disease, neurodegenerative disease, even some cancers). There is a long list of possible reasons for silent inflammation. Some which are very much unavoidable such as increasing age (reducing the stringency of our inflammatory controls) and seasonal cycles (yes, seasonal circa-annual immune oscillations do occur); and some that are very much avoidable such as smoking and leading a sedentary lifestyle. Obesity, diet, social stress, inadequate sleep,, social jet-lag, microbiome disturbances and periodontal disease (literally inflamed gums) are also thought to be relevant as are many ill-defined components of our modern environments and lifestyles. Importantly, there are few, if any symptoms of silent inflammation.

Anyone who has experienced an infection will recognise the psychological & behavioural components of feeling unwell. Clinically, these are termed ‘sickness behaviours’ categorised as lack of energy, social withdrawal, fatigue, numbness, reduced appetite, muscle & joint aches, and often dismissed as uncomfortable, but banal, components of being unwell. ‘Sickness behaviours’ are the result of neuroendocrine changes in response to our inflammatory communication molecules, the cytokines. This is all an evolutionarily conserved immune strategy to help us efficiently fight infection, forcing us to rest and temporarily withdraw from social obligations, minimising infectious spread and hastening recovery. So how does our immune system trigger these powerful behavioural changes? Contrary to what was long believed about the blood-brain barrier, our immunological chemical messengers, the cytokines can actually cross from the bloodstream into the brain, where they convey signals to neurons instructing an adaptation in behaviours to enhance recovery. Based on the scientific evidence, sickness behaviour appears to be the outward expression of a reversible episode of acute inflammation, an adaptive psychological response to biological changes. Mediated by immune system communication molecules called cytokines! Like any behaviours, sickness behaviours can become pathological for our wellbeing when out of context or when exaggerated in intensity or duration (remember inflammation is only ever meant to be short-term). We know unruly low-grade chronic inflammation is a driver of age-related disease including heart disease, and type 2 diabetes but also possibly depression.

While public awareness of mental illness is growing, the conversation has started, and the stigma is (hopefully) fading, we may not question it as a valid health concern as we once did, but frustratingly we still don’t know how best to treat it.Depression is one of the most common mental health disorders in the world with the WHO estimating that over 350 million individuals of all ages suffer with major depressive disorders and a third or all people with depression fail to respond to conventional therapies. There are substantial close similarities between symptoms of sickness behaviour when you have an infection & clinical signs of depression which have left scientists asking the question – Is depression an inflammatory disorder? Evidence supporting this possibility is emerging from both clinical research and experimental studies on depressive disorders. Overall, data (including 3 large meta-analysis) consistently report that people with major depressive disorders have significantly increased levels of inflammatory communication cytokines in their blood.

While it’s likely that there may be more going on with depression that just inflammation, we can no longer ignore it as a crucial factor that reconciles the biology of our bodies with the psychology of our minds. We still don’t know if inflammation is necessary or sufficient to produce the symptoms currently used to define depression, nor if inflammation contributes to the majority or subset of major depressive disorders. Despite this, inflammation is an incredibly useful lens through which to inform better treatment and prevention strategies and well as providing a measurable way of monitoring progression of depressive disease. Particularly since controlling inflammation shows promise as being both important for longevity and health in general. There are now clinical trials looking at anti-inflammatory omega 3 and phytonutrient rich dietary interventions, vitamin D supplementation, use of immune regulating probiotics and mind-body techniques. These are all known to reduce silent inflammation and now show promise for treatment of depression. I predict that the ultimate cure for depression will not just be a magic pill, pharmaceutical or otherwise but will be a multi-pronged intervention with a focus on influencing the levels of chronic inflammation. This might include programmes targeted at maintaining a healthy weight, avoiding a sedentary lifestyle, good quality sleep and reducing social stress while ensuring all the dietary and nutritional requirements are met for reducing inflammation.