Autoimmune Disease IV (Inflammatory mediators)


Introduction

.Let us summarize what we know so far. In general conventional medicine are still ‘grasping at straws’ and on various medical websites the statement ‘ the cause of autoimmine disease is unknown ‘. and still they have not figured out that many dis-eases are simply the bodies way of adapting to a toxic,nutrient deficient environment presented to it by the host. Some medical scientists are aware WHY autoimmune disease exists and yet the front line physicians still continue to  ‘ride the party line’ and state that the cause is unknown. Their answer ” suppress the immune system’ using Corticosteroid drugs.  Autoimmune conditions are not to be trifled with ( 23-50 million sufferers in the US alone), and some can be fatal.  

Although allopathic doctors never discuss the microbiota,  I believe most of us know how crucial this internal microbial ecosystem is to our overall health.  We discussed the importance of initial colonisation of the microbiota in the neonate gut from Mother’s breast milk that contains all necessary probiotic bacteria including Bifidobacterium (The bacterial strain that activate T and B immune system cells),  and Bifidus factor that increases growth of Lactobacillus Bifidus, another crucial member of beneficial bacteria. To protect the neonate, breast milk also contains the important components of the immune system including Leukocytes, Phagocytes and secretory Immunoglobulin A ( sIgA). We emphasised the importance of balance within the microbiota and the Host cell-Microbial interaction and symbionic crosstalk.  We discussed the immune system T cell population that are trained in the thymus gland, a general description of both innate immune system and Adaptive immune system and how tight their functional relationship is. Finally, we described the Th1 response ( cell mediated and infections ), and Th2 response ( dealing with humoral and bloodstream invasion) and how crucial both responses need to be balanced, by balancing the gut flora with probiotic bacterial strains such as Bifidobacterium Longum.  In this part we will discuss inflammatory stimulation and suppression with respect to the bodies Eicosanoids


Inflammation

Inflammation is biologically a complex process that is triggered by the body as a protective response when the body is under threat by substances that potentially can cause harm.  Typically an inflammatory response ignites heat,pain, swelling (increased permeability of blood vessels causing plasma proteins and fluid leakage into the tissue known as edema ) and blood flow stimulation ( Vasodilation or enlarging the blood vessels to increase blood flow causing redness of the skin at the trouble site). This is typical of a response from the innate immune system, that engage various chemical mediators that either promote or down regulate the inflammatory process. These mediators originate from the blood plasma and the cells of uninjured tissue and from the damaged tissue themselves.  To deal with bacterial infection of wounds or cuts a pattern recognition system called PAMPs ( Pathogen Associated Molecular Pattern ) which are located as surface receptors on immune system cells. Those involved with an inflammatory response include Macrophages, dendritic cells, Kupffer cells ( specialised macrophages resident in the liver that get activated by inflammation caused by alcohol poisoning for example), and Mast cells.


Eicosanoids

Eicosanoids are essentially signalling molecules made enzymatically or by non enzymatic oxidation  from Arachidonic acid or other fatty acids like PUFA (Polyunsaturated fatty acids ) allowing cells to communicate between each other especially during an inflammatory response. These signalling molecules are Prostaglandins, Leukotrienes, thromboxanes and others.  If you have read the article series on Metabolic typing you may remember the importance of Prostaglandin balance associated with the balance of Omega 6 and 3 essential fatty acids. I have recreated the diagram that shows this relationship below.  

Prostaglandins

Hormones, which are regulatory substances used to stimulate specific cells or tissues to function, are released from various organs that are Endocrine derived ( specific organ to a distant part of the body) system. Whereas prostaglandins behave in a similar manner but they are Autocrine/Paracrine derived ( acting on itself/acting within the vicinity or localised ) also involved within an inflammatory response scenario. The Prostaglandins are transient insofar as they are metabolised rapidly. Referring to the diagram below, it shows the Prostaglandins Series 1 (PG1) derived from DGLA, Series 2 (PG2) derived from AA and Series 3 (PG3) derived from EPA.   The fatty acid Base dietary sources are LA ( Linoleic Acid for Omega 6 ) found primarily in plant grain oil, nuts and ALA ( Alpha Linoleic Acid for Omega 3) found in plant seed oil and vegetables and some nuts. A third category is Conjugated Linoleic Acid (CLA) which is found naturally in grass fed beef and grass fed dairy. CLA is also produced in the body by bacterial conversion of LA.

Prostaglandin series 1,2 and 3

PG2 series of Prostaglandins are involved in inflammation response promotion by recruiting Mast cell and Macrophage cells to treat injury and effect repair. It also regulates the human reproduction system by inducing labor.  PG3 and PG1 series Prostaglandins are anti-inflammatory messengers that are responsible for protecting the body from heart attack and also acting as mediator for inflammatory response so one part of the Omega 6 Conversion pathway promotes inflammation ( as it has to repair the body ).  The other part of the Omega 6 pathway producing PG1 and the Omega 3 Conversion Pathway producing PG3 dampens inflammation ( once repair is complete ). PG3s provide an anti-clotting function, lowering of triglycerides ( fats in the blood), blood pressure control and the improvement of skin conditions.  Therefore there are 2 anti-inflammatory pathways and 1 proinflammatory pathway. You will notice also from the diagram certain nutrient deficiencies actually inhibit both pathways production. Another observation is the recommended 2:1 ratio which is necessary since if you swing to far in either direction ( typical ratio for people eating fast food or processed food could by 15 or 20:1)  would continuously saturate the conversion enzymes and leave nothing to activate the Omega 3 conversion pathway unless you consumed enough fish oil and/or fish eggs.  In effect you have necessary opposing systems ( an ‘On’ and ‘Off’ switch ) synonymous to the ANS Sympathetic ( On switch ) and the Parasympathetic (Off switch ).

Immune system mediators: Leukotrienes

We can modify the diagram to incorporate another Eicosanoids, namely Leukotrienes as shown below, whose functions are divided into 2 main groups. The first group are involved where neutrophils, an essential inflammation site first responder and an essential cell of the innate immune system.  Physiological dysfunction triggers the production of Leukotrienes, activating an inflammatory process such as Cystic Fibrosis, Inflammatory Bowel Disease and Psoriasis ( the latter two are autoimmune conditions). The second group are involved where basophils, and Mast immune system cells,  trigger an allergic inflammatory response igniting bronchial conditions such as Asthma.   

The ‘Take home message’ here is that not consuming enough of omega 3 essential fatty acids ( such as flax, hemp or chia seeds, fatty fish, krill oil) and too much omega 6 fatty acids ( such as butter, animal fats, organ meats, coconut and eggs) prostaglandin and leukotriene production is disrupted due to the imbalance. The deficiency of Biotin ( eggs), and Vitamins E,B12 deficiency, excessive consumption of hydrogenated oils ((Vegetable oils like soy and corn ), margarine that contains trans fat, or Oleic acid ( from Olive oil), and even nuts will inhibit the D6D (Delta 6 Desaturase) conversion enzymes. This is important if you rely on the multi-step conversion process to produce the essential immune system messenger molecules Leukotrienes and Prostaglandins. Unfortunately, biological conversion processes vary from person to person and ageing is another factor that determines its efficiency. Assuming the conversion is inefficient our gut bacteria produce Conjugated Linolenic acid which gives the host another chance to produce these inflammatory messengers, but if the gut is dysbiotic as we are focusing on during our discussion of autoimmune conditions, then this will not work either causing vital repair work not be accomplished within the body.

Conclusions

In this part I have included a discussion on general inflammation as a crucial corrective measure to bring order back into a dysfunctional body.  To eliminate the cause, repair and heal the body back to health..not ‘paper over the cracks’ by masking the symptoms hoping that everything will be alright.  The human body contains thousands of biochemical processes that all work in harmony and synchronously, and to heal, if we respect the bodies complex multi-functionality and work with the body. The immune system is vital for our survival and if it gets out of control like any chemical, electrical, electronic, system, we need to have the knowledge to correct it.  It is essential that you are aware of some of these processes that require appropriate dietary intervention such as the Eicosanoids to maintain immune system order. In the next part we will discuss immune system tolerance and explore in detail the debilitating condition of asthma and allergies, and how we can cure the INCURABLE.

– Saliva one, what have you got?|- An egg 2-20. E-Gamma-Gamma. Over.
– Any mayo?|- Affirmative.
Slow bowel traffic…
Enzyme breakdown in ten.
When I was a rookie cell,|you could eat off this place.
Look at it now. Jeez…
…what a disgrace.

Movie quotes Osmosis Jones 2001

References/Acknowledgments :

    1. Probiotics (Protection against infection) Book 2016 Case Adams
    2. Inflammation mediators The Free Dictionary
    3. What are Leukotrienes and how do they work in Asthma Abi Berger 1999 BMJ
    4. Eicosanoids, Inflammation  Wikipedia
    5. Metabolic typing Part III 2017 Article Eric Malouin, extremehealthacademy.com
    6. The role of fats in increasing and decreasing inflammation Michelle Shaughnessy 2016 Primal Nature Nutritional Therapy
    7. Movie quote Osmosis Jones 2001 Movie script SpringfieldSpringfield.co.uk

Author : Eric Malouin