Clinical PNI – What is it and what can it do for you?

PsychoNeuroImmunology (PNI)

What’s in a name?
And why such a long word?

I often wish there could be a shorter name for it but the name encompasses the complexity of what is today one of the best scientific platforms for truly integrative healthcare. What’s in a name? The clues are there. Psycho-neuro-immunology (PNI) is the science that studies how psychological aspects (thoughts, emotions and behaviours), in connection with neuro-endocrine adjustments (through hormones and other chemical substances) affect the immune system (inflammation and protection against harmful invaders).  In other words, PNI considers how your thoughts and emotions impact your brain/nervous system, your hormones and ultimately your ability to protect yourself against disease.

PNI is a science of integration, interdependence and interaction. In fact, it encompasses a lot more than those three main domains mentioned in the name. From environmental and socio-economic circumstances affecting someone’s life to molecular mechanisms that determine phenotypical gene expression, PNI is about how context and subject interact in dynamic co-existence. The immune system plays a central role due its direct relationship to defence mechanisms and its influence over energy consumption. When it comes to energy budgets and allowances in the physiological hierarchy of the body, the immune system can take over the whole system. And the logic of that is clear: in charge of decisions relating to defence mechanisms, the immune system (which is intimately integrated with the nervous system) should be able to take over and impose redistribution and reallocation of energy resources when necessary. In extreme cases of unresolved threat or danger, as in severe burning, trauma or sepsis, the immune system will sap resources in the body and eventually exhaust them. This is seen for example when people in intense care units lose weight and muscle mass in an uncontrolled manner, despite the hospital’s best efforts to keep them alive.  What ultimately kills the person is the severe and eventually uncontrollable triggering of the immune system. This is one of the extreme ends of a situation which was also confirmed in the severe COVID-19 cases leading to ‘cytokine storms’ (Ye Qing, 2020). This hyperinflammatory response is closely linked to impaired energy distribution and availability – characteristic features of conditions associated with metabolic syndrome and obesity. At the opposite end of the spectrum, the immune system may faulter in its surveillance and fail to protect us from either microbes (invaders) or malfunctioning cancerous cells (tumours). In such cases, cells can multiply uncontrollably and grow powerful enough to kill us. From a physiological perspective, the preservation of survival is the body’s highest priority, and the immune system plays a central regulatory role in determining how energetic and metabolic resources are allocated. Within this framework, chronic and unresolved metabolic challenges—whether stemming from adverse childhood experiences, poor dietary habits, or other contributing factors—must be taken seriously, as they represent key drivers of long-term immune dysfunction and disease progression.

When it comes to energy resources, the immune system could be said to have the final word.  But, the brain, also featuring highly in the hierarchy of organs, is another hungry consumer of energy, especially when compared proportionally to other parts of the body (7).  Once again, there is good logic in that: one of the reasons why humans have survived through evolution, able to thrive in so many different environments all over the planet, has to do with the size and sophistication of a hugely energy-expensive brain.  From an evolutionary perspective, prioritizing the brain makes sense, as it serves as the central processor for interpreting environmental context, modulating behaviour, and planning adaptive responses. But even the brain must yield in a fight for survival if the immune system ends up taking over In the context of acute immune challenges, such as viral infections, energy resources are reallocated to support immune function, often at the expense of cognitive performance and physical activity. This shift is familiar: during an illness like influenza, clarity of thoughts diminishes, physical energy wanes, and the drive for social interaction or purposeful activity decreases. Fatigue, lethargy, and the urge to rest are not random symptoms; they are adaptive behavioural responses driven by the immune system’s demand for energy during its effort to combat infection (2-3). This phenomenon illustrates how immune activation overrides other physiological priorities, including those of the brain. But what happens in situations where the immune system remains chronically activated, yet fails to resolve the underlying issue—such as in cases of persistent infection, autoimmune processes, or ongoing psychosocial stress? In these states, low-grade but continuous immune activation, often referred to as chronic subclinical inflammation or “cold inflammation”, can significantly affect cognitive function, energy levels, and motivation over the long term (4). There is substantial evidence that a state of chronic low-grade inflammation is involved in the aetiology of many common degenerative diseases from clinical depression to auto-immune conditions. The understanding of how symptoms, pathophysiology and energy regulation intersect within systems biology is not only appropriate but necessary (5). This is precisely where PNI offers a valuable framework that provides a coherent, evidence-based model for understanding the dynamic interplay between mind, brain, and body in both health and disease. The name itself reflects this integration, underscoring that PNI is a complex, yet scientifically grounded approach that aligns with the latest insights into how the human body functions as a unified system.

From new scientific paradigms to practical interventions that encompass the whole person

PNI is a relatively new scientific discipline that arose from the urgent need to integrate expertise from multiple fields into a unified framework focused on systemic influences and outcomes. This science acknowledges that all parts of a living organism belong to an interconnected whole, operating in concert rather than isolation. PNI was developed to help practitioners ‘zoom out’ and consider the bigger picture—examining the relationships between different body systems (including organs, mind, and emotions), the underlying logic of pathophysiology, and how these elements dynamically interact within the context of a person’s life.

In modern healthcare, it is common to experience specialists concentrating deeply on their specific areas without fully addressing how various symptoms may be linked or stem from the same systemic imbalances. Many patients notice that their symptoms are treated in isolation, leading to fragmented care that fails to account for the complex interplay of factors affecting their health. This reductionist approach often overlooks the broader biological and contextual reasons behind symptoms, resulting in treatments that often fail to acknowledge the whole person at the receiving end of treatment. Interventions may overlap, counteract each other or even lead to further symptoms. For practitioners who find themselves dealing with multiple diagnoses in isolation and struggling to harmonise treatments into one coherent approach, the emergence of practical interventions that focus on the whole person and systemic changes can bring significant improvements to long-term results.

A crucial foundation of PNI is its grounding in evolutionary biology. Despite advances in biomedical science, human physiology remains largely shaped by millions of years of slow evolutionary processes. Our genetic makeup today is nearly identical to that of humans hundreds of thousands of years ago. Understanding this helps explain why rapid environmental changes—such as drastic shifts in diet, lifestyle, and social structures over just the past few decades —can have profound impact on our health. While our bodies evolved to deal with variables and fluctuating conditions such as food insecurity, periodic physical exertion, competition for social bonds, and dependence on nature; modern life often obliterates opportunities for engagement of self-adjusting mechanisms that maintain behavioural motivation, variability of genetic expression and physiological flexibility. Moreover, processed foods, chronic stress, sedentary behaviour, and artificial environments create dysregulation of bodily processes that accumulate and overlap to create degenerative changes. The mismatch between the modern environment and the human ability to adjust to old natural challenges which helped shape our physiology raises important questions: How well can we adapt to modern living? What are the health consequences of these rapid changes? Is there a point at which constantly reliable comfort, food and hygiene become detrimental?

How should we look at chronic diseases to truly understand how to deal with them?

Evolutionary biology reveals that the body often sacrifices optimal health in favour of survival, providing insight into the development of chronic diseases. Consider insulin resistance, the precursor to type II diabetes. Rather than viewing insulin resistance simply as a malfunction, it can be understood as an adaptive response to excessive sugar and refined carbohydrate consumption in modern settings. This adaptation may even be influenced by demands placed on the immune system. Recognizing this perspective can shift our understanding of chronic disease from one of failure to one of survival strategy. Diseases that do not improve survival tend to be eliminated by natural selection, so the rising prevalence of chronic conditions in modern societies likely reflects a form of physiological response to cope with rapid environmental change. Even if that response results in illness such as chronic degenerative conditions, it might buy people time to resolve the challenges that have been left unaddressed in their lives and the symptoms that signal the need for change.

This evolutionary framework provides a valuable ‘safety net’ that helps maintain perspective on the underlying logic of symptoms and disease. The human body is an extraordinarily complex and self-adjusting intelligent system, and despite technological advances, we are still uncovering its full intricacies. Our fast-paced lives and desire for immediate solutions can lead to premature interventions that miss the complexity of systemic contexts. Our ancient biological systems cannot accelerate their adaptation to modern pressures, and disease may represent the body’s unavoidable immediate response to these challenges. If insulin resistance, obesity or depression can buy the individual time to resolve something that continuously challenges the system, these degenerative conditions may be viewed as compromises that the body is forced to make in its attempt to survive. Rather than eliminate symptoms blindly as they show up, curiosity to understand their root causes and work with interventions that allow the body to restore homeostasis would contribute to a better chance to restore health instead of simply manage disease.

A new science based on old clues

Despite the long-complicated name, psycho-neuro-immunology is more than justified. It really is as small a name as it could be since even a long name like that doesn’t do justice to the complexity involved.  Although it is so obvious that a human being is more than the collection of biological systems and physiological functions, it has taken us a long time to acknowledge the influences of the psyche, emotions and thoughts on health. Today, psychological and emotional aspects are recognised as important dimensions of mental health but the importance of this realm for physical symptoms and disease is still not well embedded into healthcare.  To this day, albeit hard to justify, the mistaken view of body and mind as separate entities in is still a reality proven difficult to reverse. Physical symptoms are no doubt different to psychological or mental-health related symptoms but the mistake lies in their separation as two unrelated domains.  There is no doubt, for example, that pain has an impact on your emotional state. That’s easy to grasp considering chronic or acute physical pain is not associated with happy feelings, a motivated attitude or positive emotions. Why then wouldn’t the reverse be true and significant as well? In the example of pain perception and associated emotions, isn’t it clear that emotional states can impact pain perception? If we recall the times in our lives when the very fact of feeling positive, motivated, happy or excited has literally dampened our perception of pain it will be easy to see how the influences between the physical and emotional realms work both ways. What about the sensation of hunger disappearing when you first fall in love? One can exist on almost thin air when first taken by the powerful emotions known to accompany the experience of ‘falling in love’.  Has anyone ever wondered why an emotional state would interfere with something as basic as the need to eat? After all, feeding and energy production is the most primitive physiological need that affects pretty much every cell and system in the body. Would it be right to say that your physiology is altered by your emotional state?  What about specific functions in the body, for example, the ability to reproduce or fight infection, how are they affected by the chemistry of emotions and stress? Do different types of emotion and psychological states have different effects on diseases? What is the biochemistry of these very clear effects we all know to exist but haven’t yet had a chance to understand? The need to answer these and many other questions is what is at the core of PNI.

The importance to connect body and mind is undeniable and many missing clues for the real solutions to many physical symptoms may be where we have neglected to look.  However, PNI is not a theoretical hypothesis, a philosophy or a ‘feel good mind-soul therapy’.  PNI is neither simplistic nor reductionist. In PNI you won’t be told ‘it is a matter of your state of mind’ nor is the solution a simple ‘think positive thoughts and everything will be OK’.  While a positive mindset will no doubt be beneficial, PNI is not about subjective interpretation nor opinions about the ‘unknown’.  PNI is grounded in objective, hard-scientific data and the application of a systems biology rational translated into practical and simple lifestyle interventions.

PNI has emerged from the dynamic integration of multiple specialised disciplines, including biochemistry, immunology, neuroendocrinology, epigenetics, various omics technologies, and evolutionary biology. Its distinctive contribution lies in being the first science to unify these diverse fields into a cohesive framework aimed at therapeutic applications, particularly in the context of chronic disease management through lifestyle interventions.

In clinical PNI, practitioners are trained to understand the physiology of disease and relate it to the evolutionary rationale that has shaped the biochemical mechanisms that justify the development of pathology. This comprehensive perspective encompasses factors ranging from intrauterine and early-life epigenetic programming to cognitive development and individual life experiences. By considering and drawing from the biological functioning of the whole person, practitioners seek to elucidate how physical symptoms and chronic illnesses manifest within an integrated system within a specific context. Therapeutic interventions are multifaceted and employed to assist individuals in recognizing connections among various physiological and emotional factors, thereby addressing systemic imbalances that underly the processes behind chronic diseases.

 What else plays a part?

Another fact that has taken long to gain respect within the modern medical understanding of health and disease is the influence of stress on the many systems of the body. Today it is not so difficult to make a point that your stress levels impact not only on how you behave and feel but also on your long term health status. The chemistry of the stress hormones in a nutshell can be summarised in one main point: redistribution of resources according to priorities. There is only so much energy available for immediate use in the body and all organs and systems have to make do with that (4).  I guess you might think we can always eat more if we need more energy but in pathological states where the immune system is active, it won’t quite work that way.  In fact, eating behaviour and digestion are examples of functions that can get dampened down by a busy immune system.  For example, how was your appetite last time you had a fever? Was eating a priority then? You can see that if things were that simple, we wouldn’t be on this growing wave of ever-increasing chronic diseases right when food has become easily available with the advent of fridges and supermarkets.  Obesity would be an advantage if we could access our energetic reserves in that way. In fact, the very nations plagued with chronic diseases such as diabetes, cancer, obesity and auto-immunity are the ones where access to food is easy and abundant.  Is there a logic in that? You bet there is and those are the kinds of connections PNI focuses on. The links between lifestyle and health status, physical exercise, diet and disease are evident and the biochemistry behind them is revealing crucial information to the correction of physiological states of imbalances. Grounded in the scientific principles of evolutionary biology and the emerging paradigms of psycho-neuro-immunology, Lifestyle Medicine is poised to continue its rapid integration into mainstream healthcare. This brings with it much-needed progression in the management of chronic disease, supported by a growing body of robust scientific evidence. It is the inevitable evolution of healthcare that must be born out of the agonising crisis it experiences today.

By Ludmila Enticott – www.celltosoul.co.uk

• BSc (First Class Hons) Nutritional Therapy (University of West London) 2012 – BANT member & CNHC Reg
• Senior Health & Wellbeing Coach – South Warwickshire GP Federation since 2020
• PgDip Clinical Psychoneuroimmunology (Natura Foundation – Netherlands) – 2017
• MSc Clinical Psychoneuroimmunology (Pruimboom Institute – International Campus – expected 2028)
• Lifestyle Medicine Practitioner – BSLM member since 2023

 References

1. Ye Qing, W. B. M. J., 2020. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. 80(6), pp. 607-613.
2. Turkheimer F E et al (2023) Sickness behaviour and depression: an updated model of peripheral-central immunity reactions. Brain Behav Immun 111:202-210.
3. Pollak Y, Yirmiya R (2002) Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol 5(4):389-99.
4. Potenza M A et al (2017) Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: current and perspective therapeutic options. Pharmacol Res 120:226-241. PMID 28408314.
5. Rainer H Straub (2015) The origin of Chronic Inflammatory Systemic Diseases and Their Sequelae. Amsterdam: Elsevier/Academic Press.
6. Straub R H, Cutolo M, Buttgereit F, Pongratz (2010) Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. Journal of Internal Medicine doi: 10.1111/j.1365-2796.2010.02218.x
7. Hitze, Britta. ‘How the Selfish Brain Organizes Its Supply and Demand’. Frontiers in Neuroenergetics, 2010. org (Crossref), https://doi.org/10.3389/fnene.2010.00007.