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Chronic inflammation and autoimmune diseases

Skin disorders, rheumatoid arthritis, polymyalgia, fibromyalgia, chronic fatigue syndrome (CFS), chronic allergies and inflammation: support and recovery strategies

A complex phenomenon

Autoimmune diseases form very broad spectrum encompassing a diversified range of disorders that vary in terms of disease severity and site of organic damage. 
As such, autoimmunity includes skin disorders such as atopic dermatitis or psoriasis, forms of chronic pain such as rheumatoid arthritis, rheumatic polymyalgia, fibromyalgia, Chronic Fatigue Syndrome (CFS), airway diseases due to allergy and inflammation (allergic rhinitis, asthma), atherosclerosis, multiple sclerosis, allergic conjunctivitis. Still, despite these clear differences, all autoimmune diseases feature chronic inflammation [9,11,16,18,19,21,31,51,58] coupled with neuroendocrine alteration that prevents the extinction of the inflammatory hotspot. All of the above-mentioned diseases show increased expression of proinflammatory cytokines such as IL-2, IL-6 and TNF-α [8,60] and inflammatory markers (such as the C-reactive protein) [15].  
Studies consistently report a deficit in the immunoendocrine axis response in patients with these diseases and a resulting difficulty or impossibility in curbing the inflammatory activity underway. [1,10,15,26-28,31,41,43-45,49,51,53,56,59,62]


Figure 1: the immunoendocrine axis response is unable to mitigate inflammation

Cortisol and ACTH baseline levels do not seem to significantly differ between patients and controls. Instead, cortisol/CRP and ACTH/CRP ratios have been found to collapse. In addition, the stimulation test done with ACTH produces a significantly mitigated response in terms of cortisol release. [5,24,36,47] 
A hallmark of autoimmunity is a flat low HPA axis (HPA axis index: Flat Low, BIA-ACC) or in any case a flat low adrenal cortex (this being the ultimate trigger of the HPA axis). In addition to poor secretion of cortisol in response to stressors, a degree of resistance or inertia that slows down the restoration of baseline cortisol levels has also been found. The latter plays a role in the disruption of the circadian rhythm of the neuro-immunoendocrine axis and frequent arrhythmic lowering and flattening of baseline plasma cortisol levels, often worsened by thyroid function inhibition (hypophysis lowering of TSH and GH). [12,22,29,30,37,40,54]


Figure 2: response to a stressor in a healthy individual as compared to one with autoimmunity

Still, it seems that the alteration of the HPA axis and its interactions with the sympathetic nervous system (PPG Stress Flow) cannot be properly described by generically labelling them as being flat low. Indeed, with the hypothalamus and the release of CRH, the situation can be the opposite, with excess (proinflammatory) central and peripheral CRH [6,35,48,52,63] that, in turn, correlates to decreased TSH and GH. Other experiences provide information on the increase in baseline noradrenaline (due to overstimulation of the Sympathetic Nervous System - SNS) and the response of noradrenaline to inflammatory stimuli (in particular to increased IL-6) in patients with fibromyalgia [2,3,38,50], which highlights an altered regulation of the sympathetic nervous system (post-stress increase in the heart rate, inhibited insulin secretion, altered thermoregulation, etc.).

Autoimmunity-related issues:


Recovery strategies

As such, whatever the cause, autoimmune diseases are triggered by inflammation, the inability of the neuro-immunoendocrine reaction to mitigate and eventually extinguish inflammation, resulting in damage to healthy tissues. 
Clearly, it is necessary to limit the damage produced by chronic inflammation. It is therefore fundamental to take into consideration the degree of systemic inflammation (that can be evaluated through: ECW extracellular water - BIA-ACC, RMSSD vagal activity and capillary permeability - PPG Stress Flow) and to adopt strategies that are suitable to progressively curb it so as to reduce the incidence, or at least the intensity, of symptoms. 
By integrating very useful information, it is possible to swiftly restore major biological rhythms lost due to chronic inflammation. 
The main goal is to create rhythmicity, in biological, physical and metabolic terms, between the acrophase and the batiphase. The dominance of the sympathetic nervous system (LF range – sympathetic nervous system – PPG Stress Flow) during the day and the dominance of the parasympathetic nervous system (HF range – parasympathetic nervous system – PPG Stress Flow) in the evening enables to ensure this rhythmicity. 
Besides, adding, as appropriate, buffer systems supplements is useful to counter the subclinical acidosis that is typically associated with chronic inflammation.
A negative PRAL diet that takes into account the proper glycemic load (GL) between day and night, is equally useful to counter subclinical the acidosis associated to inflammatory load, while strongly supporting the acrophase (nervous system and cortisol in synch). 
In view of mitigating inflammation, besides stimulating the immunoendocrine system, one should consider taking omega-3 poly-unsaturated fatty acids: EPA and DHA are particularly indicated for suppressing the inflammatory processes correlated to autoimmune diseases, mainly by inhibiting the synthesis of  arachidonic acid derived proinflammatory eicosanoids (omega-6). [13,20,23,25,33-34,39,42,46,61]. As a matter of fact, many have demonstrated a decrease in the main inflammatory markers (in particular IL-6 and TNF-α) as a result of taking these omega-3 supplements. [23,66] 
Recent studies [7,14,17,64] have shown the anti-inflammatory properties of hops extracts (Humulus lupulus L.) as proven by lower CRP, particularly in treating chronic pain such as rheumatoid arthritis and other diseases associated to chronic inflammation coupled with chronic stress.

Authors: Dario Boschiero, Mariantonietta Lucafò - Date: 22/02/2021

Attention: these contents can be freely used for personal learning purposes only. The use is regulated by Law No. 633/1941 and subsequent amendments, as well as by the copyright and patent legislation in force. Any use for commercial and profit-making purposes is forbidden.

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