Multiple Chemical Sensitivity Etiology

Airway Genetics and Ambient Combustion Aerosol

MCS has airway genetics as a factor in most cases.

 VERONESI B. AND OORTGIESEN M. NEUROGENIC INFLAMMATION AND PARTICULATE MATTER AIR POLLUTANTS. NEUROTOX 22;795-810 2001: 

"...taken together, the above in vivo and in vitro studies suggested that the variable inflammatory sensitivity to PM observed in different mouse strains (ie Balb/C, B6) related to quantitative differences in the neuropeptide, VR1 (now TRP) receptors and acid sensitive pathways found on sensory neurons that innervate the nasal and upper pulmonary airway. Such data showed how genetically determined differences in sensory neural pathways could influence expressions of PM-induced airway inflammation...genetic differences are thought to underlie these variations and have been experimentally demonstrated for ozone (Kleeberger 1995, Zhang et al 1995), nitrogen dioxide (Holroyd et al 1997), and diesel exhaust (Ichinose et al 1997, Miyabara et al 1998)..."

VERONESI B. ET AL VANILLOID CAPSAICIN RECEPTORS INFLUENCE INFLAMMATORY SENSITIVITY IN RESPONSE TO PARTICULATE MATTER. TOX APPL PHARM 15;169(1): 66-76 2000:

"...DRG neurons, cultured from BALB/c and B6 neonates, were loaded with Fluo-3 AM and exposed to the prototype irritants, acid pH (5.0, 6.5), or capsaicin (3, 10 μM). Analysis of their increases in intracellular calcium showed that significantly higher numbers of BALB/c neurons responded to these prototype irritants, relative to B6 neurons.

Morphometric analysis of BALB/c neurons, histochemically stained with cobalt to label neurons bearing capsaicin-sensitive receptors, showed a significantly higher level of stained neurons relative to B6 neurons.

Finally, semiquantitative RT-PCR showed a higher expression of VR1 receptor mRNA in DRG and spinal cord taken from neonatal BALB/c mice relative to B6 mice.

Taken together, these data suggest that capsaicin and acid-sensitive irritant receptors, located on somatosensory cell bodies and their nerve fiber terminals, subserve PM-induced airway inflammation and are quantitatively different in responsive and nonresponsive mouse strains..."

ROY ET AL. SUSCEPTIBILITY TO POLLUTANT-INDUCED AIRWAY INFLAMMATION IS NEUROGENICALLY MEDIATED EPA EIMS METADATA REPORT 59754 2000:

"...We have previously shown that the BALB/c mouse strain is responsive to PM-inflammation in contrast to the non-responsive C57/blk (B6) mouse strain.

This differential sensitivity is retained in PM exposed cultures of somatosensory neurons from the dorsal root and trigeminal ganglia that innervate the airways in terms of inflammatory cytokine release.

In the present study, we use RT-PCR, cobalt histochemistry and immunocytochemical techniques to show that the  expression of capsaicin (VR1) and Substance P (NK-1) receptors and the release of inflammatory cytokines and neuropeptides are higher in sensory neurons from BALB/c mice relative to the  B6 strain. 

These data suggest that the strain-specific inflammatory response to PM and other irritants (i.e. capsaicin, acid sensitive) seen in vivo and in vitro models of PM inflammation is subserved by sensory  and neuropeptide receptors..."

Heritability of respiratory symptoms has been shown.

ELBERLING J. ET AL. A TWIN STUDY OF PERFUME-RELATED SYMPTOMS. INT J HYG ENV H 212: 670-78 2009

"In conclusion, we found an increased familial occurrence of perfume-related respiratory symptoms where 35% of phenotypic variation was due to additive genetic effects and 65% was due to individual specific environmental effects". 

In 1921, one of the founders of psychology, C.G. Jung published Psychological Types (Princeton University Press and in the Portable Jung Viking Press) - a framework of character portraits - attitudes of introversion and extraversion and functions of feeling, thinking, sensation, and intuition. He had 8  types with each of the 4 functions paired with either introversion or extraversion. From the predominant use of one function a corresponding character portrait tends to emerge.

He reported that the introverted intuitive had an extraordinary dependence on sense impressions as a counterweight to the rarified air of the intuitive cast of mind...with hypersensitivity of the sense organs and hypochondriacal symptoms. Jung didn't know this was actually a physical disease - MCS.

 Jung recognized that each person's psychological portrait has a genetic foundation as do physical characteristics - strong evidence that MCS has a genetic basis: the vulnerability of the C-fiber nerve lined airway is greater in the introverted intuitive -  tight junction defects and focal desquamation of the epithelium exposing the nerves.

MEGGS W.J. HYPOTHESIS FOR INDUCTION AND PROPAGATION OF CHEMICAL SENSITIVITY BASED ON BIOPSY STUDIES. EHP 105:2;473-78 1997:

....There are defects in the tight junctions between respiratory epithelial cells, focal desquamation of the epithelial cells in places, hypertrophy of glandular structures, lymphocytic infiltrates, and proliferation of sensory nerve fibers...tumor necrosis factor is produced by lymphocytes....

References

ELBERLING J. ET AL. A TWIN STUDY OF PERFUME-RELATED SYMPTOMS. INT J HYG ENV H 212: 670-78 2009

Holroyd K. et al. Genetic modeling of susceptibility to nitrogen dioxide-induced lung injury in mice. Am J Physiol 273;1-3:L595-602

Ichinose T. et al. Murine strain differences in allergic airway inflammation and immunoglobulin production by a combination of antigen and diesel exhaust particles. Tox 122;3:183-92 1997

Jung C.G.. Psychological Types. Princeton University Press and in the Portable Jung Viking Press. Trans R.F.C. Hull or online Baynes Translation 1921

Kleeberger S. Genetic susceptibility to ozone exposure. Tox Lett 82-83:295-300 1995

MEGGS W.J. HYPOTHESIS FOR INDUCTION AND PROPAGATION OF CHEMICAL SENSITIVITY BASED ON BIOPSY STUDIES. EHP 105:2;473-78 1997

Miyabara Y. et al. Murine strain differences in airway inflammation caused by diesel exhaust particles. Eur Resp J 11: 291-98 1998

ROY ET AL. SUSCEPTIBILITY TO POLLUTANT-INDUCED AIRWAY INFLAMMATION IS NEUROGENICALLY MEDIATED EPA EIMS METADATA REPORT 59754 2000

VERONESI B. AND OORTGIESEN M. NEUROGENIC INFLAMMATION AND PARTICULATE MATTER AIR POLLUTANTS. NEUROTOX 22;795-810 2001

VERONESI B. ET AL VANILLOID CAPSAICIN RECEPTORS INFLUENCE INFLAMMATORY SENSITIVITY IN RESPONSE TO PARTICULATE MATTER. TOX APPL PHARM 15;169(1): 66-76 2000

Zhang L. Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice. Exp Lung Res 21;4:503-18 1995

 

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