MCS 6 Neurogenic Inflammation: Delayed Effects

[michael edward badolato jr]

If overlapping exposures are eliminated so the effect of each can be recognized - it becomes clear that there is often a 36 to 48 hour peak in symptoms after the exposure.

Guinea pigs reached a peak in nerve fiber density 24 to 48 hours after the exposure returning to near baseline at 96 hours. CASTRANOVA ET AL. PULMONARY ALTERATIONS ASSOCIATED WITH INHALATION OF OCCUPATIONAL AND ENVIRONMENTAL IRRITANTS. INT IMMUNE 2:163-72 2002.

Delayed effects can be expected for exposures involving particulate matter (PM) or certain gases. Especially potent stimulators of C-fiber nerves include nicotine and other components of tobacco smoke and residue; and the hydroxyl radical in the gas phase of woodsmoke. LEE L. & PISARRI T.E. AFFERENT PROPERTIES AND REFLEX FUNCTIONS OF BRONCHOPULMONARY C-FIBERS. RESP PHYS 125:47-65. 2001.

Combustion byproducts from motor vehicles and exposure to print also result in a 36 to 48 hour peak.

Most total and delayed symptoms result from tobacco and detergent residue emanating from clothing and second hand smoke that may be present in buildings - along with combustion byproducts of the ambient air common to both outside and interior spaces.

Olfactory nerves are those of smell connecting to the olfactory bulb - while c-fiber nerves - also called sensory or chemical irritant receptors - connect to the trigeminal nerve.

A troublesome aspect of combustion derived and other 2 phase particulate ( as may arise from print on a page) is described in the following from VERONESI B. & OORTGIESEN M. NEUROGENIC INFLAMMATION AND PARTICULATE MATTER (PM) AIR POLLUTANTS. NEUROTOX 22;795-810 2001:

"...PM may be affecting toxicity through a more common physiochemical mechanism...acidic micro-environments associated with negatively charged colloidal PM particles, activated acid-sensitive receptors and pathways located on airway target cells. This neurogenic activation resulted in an immediate influx of calcium, which in turn, caused both the release of neuropeptides from sensory terminals and a more protracted release of inflammatory cytokines from sensory neurons...the pro-inflammatory cytokines IL-6, IL-8, TNF alpha..."

The pro-inflammatory cytokine TNF alpha may be the cause of queasiness associated with exposure.

From EMCH ET AL. TNF ALPHA ACTIVATES SOLITARY NUCLEUS NEURONS RESPONSIVE TO GASTRIC DISTENSION. AJP GASTRO & LIV PHYS 279(3)G582-86 2000:

"...it is likely TNF alpha inhibits gastric motility by directly affecting the sensitivity of gastric vagal control circuitry in the medulla. This vago-vagal reflex circuit is outside the blood brain barrier and therefore is readily accessible to large circulating peptides. Additionally TNF alpha increases vascular-brain permeability and TNF alpha may gain access to the brain through a specific transport system..."This inhibition of gastric motility or stasis is perceived as queasiness or nausea.

If one should consider how the airway could have such far reaching effects - Rebecca Bascom posed the question.

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

"...multiple chemical sensitivity represents an amplification of the non-specific immune response to low level irritants. This alteration may occur through altered function of the C-fiber neurons, an altered function of the respiratory epithelium, or an altered neuro-epithelial interaction...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...

More recent research continues to affirm the airway originating effects.

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

"...PM exposure is associated with...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...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..."

Particulate matter (PM) consists of chemical attached to a very fine particle core - smaller than approx 75 on the tip of a pin - 10 microns down to less than .1 micron in diameter. For example, if smoking has taken place in a room and the smoke has cleared - PM as residue will emit from furnishings for months or years depending on the degree of contamination. Even with vehicle exhaust unseen - the most significant components of exposure are the fine particles especially in delayed effects. Researchers have focused on particulate matter (PM) in recent years. They recognize ambient PM levels correlate closely with increased daily morbidity and mortality.

 

References

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

CASTRANOVA ET AL. PULMONARY ALTERATIONS ASSOCIATED WITH INHALATION OF OCCUPATIONAL AND ENVIRONMENTAL IRRITANTS. INT IMMUNE 2:163-72 2002

EMCH ET AL. TNF ALPHA ACTIVATES SOLITARY NUCLEUS NEURONS RESPONSIVE TO GASTRIC DISTENSION. AJP GASTRO & LIV PHYS 279(3)G582-86 2000

LEE L. & PISARRI T.E. AFFERENT PROPERTIES AND REFLEX FUNCTIONS OF BRONCHOPULMONARY C-FIBERS. RESP PHYS 125:47-65. 2001

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

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