Multiple Chemical Sensitivity Etiology

Airway Genetics and Ambient Combustion Aerosol

Veronesi 1998 - recently located 7 months after this forum was posted - is perhaps a most insightful article concerning contact hypersensitivity. It may read Greek - but after study somewhat profound.

VERONESI B. ET AL. NEUROPEPTIDE DENERVATION ALTERS BOTH THE ELICITATION AND INDUCTION PHASES OF CONTACT HYPERSENSITIVITY IN MICE TOX APPL PHARM 153:243-9 1998:

"...In the induction phase of CHS, a chemical (i.e. hapten) is physically applied to the dermal surface and penetrates the stratum corneum. During the next 24 h, the hapten combines with host cell proteins to form a complete antigen, which is subsequently contacted and processed by Langerhans cells (LC). These LC process antigen and migrate, via the afferent lymphatics, to draining lymph nodes, where the antigen is presented to T-lymphocytes. Upon subsequent exposure to the chemical (i.e. challenge or elicitation phase), the sensitized lymph node cells (LNC) travel to the site of chemical contact and produce the characteristic skin reaction...

...chemical sensitization has been associated with distinct cytokine profiles interleukin IL-1 beta, IL-2, IL-4, IL-10, interferon gamma, and tumor necrosis factor TNF alpha measured in the draining lymph nodes...

...the skin is heavily innervated by sensory nerve C fibers which release neuropeptides (i.e. tachykinins) in response to a variety of stimuli (heat, cold, vibration, and chemical irritation). Once released, these neurotransmitters interact with immune (e.g., LC, mast cells, and lymphocytes) and nonimmune (keratinocytes and vascular endothelium) cells and influence many events associated with CHS (e.g. vasodilation, cellular infiltration, cytokine production and T-cell activation...

...Neonatal denervation with capsaicin effectively destroys over 50% of neuropeptide containing sensory neurons and their fibers. This deprives the developing immunocytes in primary and secondary lymphoid organs of critical neuroimmunological cues...

...The present data, using the neonatal model of denervation, argue that a developmental alteration underlies the signs of heightened CHS. Possible developmental effects might include the loss of neuropeptide transmitters signalling to the developing immunocytes, which would render the LNC more activated, perhaps in a different G phase of mitosis...

...a complex network of cytokines, neuropeptides, and their target cells interacts in the induction, elicitation and regulation of CHS...

...neuropeptides that are affected by capsaicin-denervation (e.g. substance P [SP], calcitonin gene related protein [CGRP], neurokinin A, and vasoactive intestinal protein [VIP]...

...Depletion or an imbalance of vasoactive peptides such as those carried by the capsaicin sensitive fibers (i.e. SP, CGRP), would alone be sufficient to change the flow of lymph and lymphocyte traffic, lengthening the time allowed for lymphocyte sensitization and enhancing the expression of CHS..."

The authors conclude that where sensory neuropeptide innervation is impaired or altered - by genetics, disease, or chemical exposure - contact hypersensitivity might occur.

The general principles of complexity above - may also apply to the neuroimmunological cues from genetically distinct airway sensory nerves in the etiology of MCS (Badolato MCS 15, Veronesi 2001).

 

Referred to earlier (MCS 5MEGGS W.J. ARCH ENV H 54(5) 309-11 1999:

 "...The mechanism by which inflammatory conditions are provoked by chemicals is via chemoreceptors on sensory nerve C-fibers with the release of substance P and other mediators of neurogenic inflammation...progression of inflammation to organ damage is possible to those who continue to be exposed..."

This was in reference to the c-fiber airway nerve (neurogenic) basis of most MCS cases. However it is also true that these same nerves and mediators of inflammation are involved with skin reactivity and fibromyalgia.

BENNETT R. FIBROMYALGIA INFORMATION FOUNDATION. www.myalgia.com/pain_amplification/scientific_studies.htm:

"...neurogenic inflammation is now understood in terms of impulses in type c-fibers evolving the release of histamine, substance P, and inflammatory cytokines from nociceptors in the skin...a 3 fold increase of substance P in the CSF (cerebrospinal fluid) of fibromyalgia patients compared to controls...substance P as a major etiological factor in central sensitization...a four fold elevation of NGF (nerve growth factor) in the CSF of fibromyalgia patients. (Substance P and NGF were found elevated in the plasma of MCS people in the Kimata study MCS 2)...temporal summation of nociceptive impulses at the level of the spinal cord normally occurs when unmyelinated c-fiber input exceeds a rate of one impulse every 2-3 seconds...a critical event in the development of central sensitization..."

 

ZIMMERMAN M. PATHOPHYSIOLOGICAL MECHANISMS OF FIBROMYALGIA. CLIN J PAIN 7: 1: s8-15 1991:

"...neurogenic inflammation induced by the release of substance P and other neuropeptides from the peripheral nerve endings may result in chemical sensitization of nociceptors..."

 

ENESTROM ET AL. DERMAL IgG DEPOSITS AND INCREASE OF MAST CELLS IN PATIENTS WITH FIBROMYALGIA - RELEVANT FINDINGS OR EPIPHENOMENA? SCAND J RHEUMATOID 26:4; 308-13 1997:

 "...these findings support the hypothesis of neurogenic inflammation involvement in fibromyalgia..."

 

KIM S.H. SKIN BIOPSY FINDINGS: IMPLICATIONS FOR THE PATHOPHYSIOLOGY OF FIBROMYALGIA. MED HYP 69: 1; 144-47 2007:

 "...the dysfunction of descending antinociceptive pathways and low hypothalamic - pituitary - adrenal function...cutaneous nerves connect to the spinal cord and/or brain...the skin is an extension of the brain...the amount of pressure stimuli required to cause cerebral activation in pain processing regions of the brain was much lower...may be related to a decrease in the activity of descending, antinociceptive pathways..."

 

BERG N.D. ET AL. NON-ALLERGIC CUTANEOUS REACTIONS IN AIRBORNE CHEMICAL SENSITIVITY - A POPULATION BASED STUDY. INT J HYG ENV H 214; 239-45 2011:

 "...also of interest are the findings from a recent study where the concentrations of several proinflammatory cytokines including interferon gamma in the blood plasma from individuals with MCS (n=77) were statistically different  from those measured in healthy controls (n=52) (Deluca et al 2010). This might prove to be a mechanism involved in the relations between airborne chemical sensitivity and non-allergic and allergic cutaneous reactions as it well known that interferon gamma drives a TH1 response that is implicated in contact allergy (Adkis et al, 2008)..."

 

Berg 2011 also alludes to other proposed explanations including variations in the cytokine and chemokine response to irritants, capacity to cope with oxidative stress, a non specific immunological response causing a vascular or neurovascular response, and a hypereactivity of the nervous system to external stimuli.

Considering high levels of cytokines, chemokines, and growth factors throughout these studies - it would seem conceivable that skin contact hypersensitivity and fibromyalgia could result from systemic oxidative stress. Possibly there are additional genetic factors involved - maybe predisposed vulnerability into altered regulation of inflammatory response specific to these areas - a more genetically sensitive nervous system which  is prone to alteration and an acute inflammatory response from breathing toxic substances or even touching them.

 

References

MCS 5 mcsmultiplechemicalsensitivity.ning.com 2012 

MCS 15 mcsmultiplechemicalsensitivity.ning.com 2012 

BENNETT R. FIBROMYALGIA INFORMATION FOUNDATION. www.myalgia.com/pain_amplification/scientific_studies.htm

BERG N.D. ET AL. NON-ALLERGIC CUTANEOUS REACTIONS IN AIRBORNE CHEMICAL SENSITIVITY - A POPULATION BASED STUDY. INT J HYG ENV H 214; 239-45 2011

ENESTROM ET AL. DERMAL IgG DEPOSITS AND INCREASE OF MAST CELLS IN PATIENTS WITH FIBROMYALGIA - RELEVANT FINDINGS OR EPIPHENOMENA? SCAND J RHEUMATOID 26:4; 308-13 1997

KIM S.H. SKIN BIOPSY FINDINGS: IMPLICATIONS FOR THE PATHOPHYSIOLOGY OF FIBROMYALGIA. MED HYP 69: 1; 144-47 2007

MEGGS W.J. ARCH ENV H 54(5) 309-11 1999

VERONESI B. & OORTGIESEN M. NEUROGENIC INFLAMMATION AND PARTICULATE MATTER (PM) AIR POLLUTANTS. NEUROTOXICOLOGY (22):795-810 2001

VERONESI B. ET AL. NEUROPEPTIDE DENERVATION ALTERS BOTH THE ELICITATION AND INDUCTION PHASES OF CONTACT HYPERSENSITIVITY IN MICE TOX APPL PHARM 153:243-9 1998

ZIMMERMAN M. PATHOPHYSIOLOGICAL MECHANISMS OF FIBROMYALGIA. CLIN J PAIN 7: 1: s8-15 1991

Views: 208

Reply to This

© 2024   Created by michael edward badolato jr.   Powered by

Badges  |  Report an Issue  |  Terms of Service