Airway Genetics and Ambient Combustion Aerosol

SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation

SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation

Links: 35 CAR Test SPC Questions
CAR Warm Up
SPC 1 Introduction: South Pole CAR (SPC) - A Character Test
SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop
SPC 3 ACA PM and ME/CFS: Do We Hear An Echo?
SPC 4 ACA UFPM: In the RBC - Through the BBB
SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS
SPC 6 ACA UFPM: Nerve Penetration
SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS
SPC 8 ACA PM: Gastro-Inflammation, Immunity, Vagal Circuitry
SPC 9 Veronesi: Sensory Nerve Insight
SPC 10 Kimata: Histamine Warning - Return to Masking
SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

On CAR
SPC 12 Disease Conditions Begin: Airway Epithelial Injury
SPC 13 Exposed Sensory Nerves - TRPA1
SPC 14 Exposed TRPA1: Central Sensitization
SPC 15 ACA: Loud and Clear
SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation
SPC 17 Calderon-Garciduenas: Airway to Systemic: Putting It Together
SPC 18 Airway Gaps - Exposed Nerves - UFPM to the CNS
SPC 19 ACA PM: Months and Years Residence Time
SPC 20 Airway Gaps: Reduced Detox Enzyme Intervention
SPC 21 Solvents and Pesticides Primary: Shoe Fits Glove?
SPC 22 Veronesi and Roy: Genetic Difference in Airway Sensitivity

SPC 23 Jung Was Right Sort Of
SPC 24 Veronesi and Jung: A Perfect Match
SPC 25 Tailpipe and Chimney Emissions: Horizontal Coning
SPC 26 How Far Symptoms Travel: 25 Years, 500 Locations, 22 States
SPC 27 Not Into That Kind of Entertaining
SPC 28 Does it Cost More Than Money?
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
SPC 30 Airway to systemic: Dysfunction of Detox Enzymes - Khatsenko
SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?
SPC 32 Phase I and II Detox Enzymes Defined

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation

Please choose the Incorrect Statement

SPC 16a)

BASCOM R. MULTIPLE CHEMICAL SENSITIVITY: A RESPIRATORY DISORDER. TOX IND H 8(4);221-28 1992:

"...the airway epithelium and the airway surface fluid it produces and regulates are the first line of defence against the multiple, "non-self" constituents in the 10-20,000 liters of air inhaled each day. The airway epithelium is not an inert barrier, as was once thought, but contains a great capacity for xenobiotic metabolism...the observation that the airway can release cytokines...flu-like symptoms, low grade fever, and fatigue that...usually begin several hours after the exposure and last up to 48 hours...a type of acute phase response. Cytokines are now recognized as responsible..."

SPC 16b)

DANTOFT 2014:

"...plasma levels of IL-1 beta, IL-2, IL-4, and IL-6 were found to be statistically significantly increased in MCS, TNF alpha was borderline enhanced, whereas IL-13 was downregulated..."

SPC 16c)

VERONESI 2001:

"...In all instances, sensory neurons release 10-200 fold higher levels of IL-6 (pro-inflammatory cytokine) relative to epithelial cells... Found elevated in MCS patients (Dantoft 2014)...conditions associated with chemical pollutants are characterized by damage to the epithelial barrier that lines the airways. Such damage not only results in the loss of critical neuropeptide deactivating enzymes (e.g. NEP) but allows the sensory fiber to physically extend closer to the airway lumen and in closer proximity to the inhaled PM particles...enhanced and prolonged inflammatory events...increased inflammatory response...

...BALB/c mice were deenervated of polymodal sensory c fibers by neonatal capsaicin treatment. Sensory neurons , dissected from the DGR (dorsal root ganglia) of these deenervated animals and exposed to various PM (50mg/ml) or prototype irritants failed to release IL-6 in response - implicating the sensory c fibers as critical to cytokine release in response to PM..."

SPC 16d)

MOHANKUMAR S.M.J. ET AL. PARTICULATE MATTER, OXIDATIVE STRESS, AND NEUROTOXICITY 29;479-88 2008:

"...acute CAPs (concentrated air particles from an urban community) exposure stimulate increases in cytokine levels in the nasal passages (Reichelman 2004)...after multiple exposure, the inflammatory cytokines may have enough time to enter systemic circulation and become detectable Found elevated in MCS patients (Dantoft 2014)...it is known that sub-chronic PM exposure produces pulmonary inflammation which results in systemic cytokine levels (Ruckerl 2007)...PM exposure is associated with pulmonary inflammation and the release of inflammatory cytokines and mediators from respiratory epithelia into the systemic circulation...

...Recent studies indicate that microglia can activate in response to circulating cytokines from the periphery and endogenous transmitters. Microglia located in proximity to fenestrated or "leaky" blood brain barriers can be signalled by circulating PM particles themselves or by inflammatory cytokines/chemokines being released systemically from the chronically inflamed airways...IL-1 is produced by respiratory epithelia in response to PM exposure... Found elevated in MCS patients (Dantoft 2014) can cross the blood brain barrier...prolonged increases in IL-1 levels causes the blood brain barrier to become leaky providing access to IL-1 and other circulating cytokines..."

SPC 16e)

MUKAE 2001:
"...We conclude that repeated exposure to PM-10 (particulate matter less than 10 microns in diameter) stimulates the bone marrow to increase the production of polymorphonuclear leukocytes (PMN) in the marrow and accelerate the release of more immature PMN into the circulation. The magnitude of these changes was related to the amount of particles phagocytosed by alveolar macrophages..."

HOGG 2009:

"...alveolar macrophages, epithelial and other cells interact with the particles to produce a wide variety of cytokines and chemokines that generate a local inflammatory immune response. These mediators spill over into the blood to stimulate the bone marrow to increase the release of leukocytes from the marrow, and the liver to increase the production of a variety of acute phase proteins. This systemic response is associated with vascular activation and the progression of the atherosclerotic process..."

ACA PM induced release of inflammatory cytokines including IL-1 beta and IL-6 from alveolar macrophages, epithelial cells, and exposed sensory nerves in damaged airway epithelium - found elevated in MCS and ME/CFS (Dantoft 2014, Maes 2012) - stimulate the bone marrow to increase output of platelets and polymorphonuclear leukocytes (PMN), accelerate more immature PMN (band cells) into the circulation prone to sequestration in microvascular beds - and increase the liver output of acute phase proteins including fibrinogen, CRP, and C-reactive protein - all associated with vascular activation and the extent of atherosclerosis (Hiraiwa 2014, 2013, Hogg 2009, Goto 2004, Mukae 2001) - and indicated by elevated PMN-elastase, lysozyme, and neopterin confirmed in ME/CFS (Maes 2012).

16f)

DELUCA 2010:

"...Notwithstanding the absence of genetic defects in CYPs, recent studies have increasingly implicated various inflammatory stimuli, first of all, pro-inflammatory cytokines (Chun 2002, Nadin 1995, Tapner 1996, Tinel 1999) to cause changes in the activities and expression levels of CYPs through nitric oxide signalling (Chun 2002, Stadler 1994). For example, drug metabolizing CYPs such as CYP3A4 and CYP2B6, which are constitutively expressed in human mono nuclear cells, have been significantly repressed by IFN Gamma or IL-2 (Liptrott 2009)...

Our results suggest that serious and multiple dysfunctions of chemical defense systems found in MCS patients may mainly not depend on genetic defects, but instead may rely on non-genetic modifications of metabolizing/antioxidant enzyme expression and/or activity, mediated by redox active agents such as NO and inflammatory cytokines..."Found elevated in MCS patients (Dantoft 2014, Deluca 2010)

"...Dysfunction of two major antioxidant enzymes and depletion of glutathione inevitably leads to severe oxidative stress and impaired elimination of phase 1 oxidation metabolites. Excessive amounts of hydrogen peroxide due to catalase deficiency will initiate a non enzymatic free radical driven chain reaction of lipid peroxidation implicated in a number of human pathologies..."

SPC 16g)

Veronesi evidenced the critical role of airway sensory c-fibers initiating the MCS disease process.

SPC 16h)

Conclusions of top researchers disregarded - MCS people do not have airway inflammatory cytokine release - systemic implications - in response to PM of the ACA.

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

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SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation

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