NYC-WTC_000199644

NYC 9/11 Public Portal Document

-.2

ResearchMS J

I ' ..15 Neurogenic Inflammation and Sensitivity to and infiltrates of leukocytes. A number of cbcmicaJ mediators of inflammation have Environmental Chemicals been identified biochemically. Inflam­ mation may be triggered by the immune William J. Meggs system, in which foreign materials inter. Department of Emergency Medicine, East Carolina University School of Medicine, with leukocyte receptors created after « Greenville, NC 27858 USA sensitizing exposure to trigger an inflam­ matory cascade. Neurogenic inflamma­ Neurogenic inflammation as a pathway dis- Sensitivity co environmental chemicals in tion is a well-defined process by which tinci from antigen-driven, immune-mediat­ general, and in panicular to volatile organ­ inflammation is triggered by the nervous ed inflammation may play a pivotal role in ic chemicals (VOCs) in indoor air, needs system. understanding a broad class of environmen­ to be elucidated. The lack of an estab­ Early in the study of neurogenic in­ tal health problems resulting from chemical lished mechanism to explain how exposure flammation, chemical stimulation was rec­ exposures. Recent progress in understand­ to concentrations of VOCs that are well ognized as a trigger of neurogenic inflam­ ing the mediators, triggers, and regulation of tolerated by the population at large can mation. As early as 1910, it was reco. - neurogenic inflammation is reviewed. Ev­ idence for and speculations about a role for produce the array of symptoms seen in nized that the application of mustard o,. neurogenic inflammation in established dis­ sensitized individuals has hampered pro­ to the conjunctival sac in experimental orders such as asthma, rhinitis, contact der­ gress in understanding these disorders. models produces inflammation that can be matitis, migraine headache, and rheumatoid Over the past few years progress has been blocked by sensory nerve ablation {1,2}. arthritis are presented. The sick building made in understanding neurogenic in­ The neuropeptides substance P (SP), neu- syndrome and multiple chemical sensitivity flammation, chemical irritant receptors, rokinen A (NA), and calcitonin gene-relat­ syndrome have been defined as clinical enti­ and the regulation of neurogenic inflam­ ed peptide (CGRP) are now known to ties in which exposure co chemical inhalants mation. Here I review these topics, coexist in sensory neurons and to have gives rise to disease. Current data on the emphasizing those aspects that may be potent vasodilatory properties (3-6). existence of chemical irritant receptors in applicable co elucidacing the mechanism Direct stimulation of sensory nerves pro­ the airway and skin are discussed; neuro­ genic inflammation arising from stimulation of chemical sensitivity as a disorder of the duces vasodilatation {7,8), which can be of chemical irritant receptors is a possible regulation of neurogenic inflammation. blocked by depletion of substance P with model to explain many of the aspects of Possible application to specific clinical capsaicin {9-11). The sensory fibers chemical sensitivities. Key u/ereii: asthma, entities is discussed, with suggestions for involved in neurogenic inflammation have indoor air pollution, multiple chemical sen- clinical research to study the association. been identified as C-fibers with a slow sidvity syndrome, neurogenic inflammation, velocity of 1-2 m/sec {12). neutral endopeptidase, reactive airways dys­ Neurogenic Inflammation Progress has been made in understand­ function syndrome, reactive upper airways Inflammation is an abnormal condition of ing the regulation of neurogenic inflam­ dysfunction syndrome, rhinitis, substance P, redness, swelling, heat, and pain localized mation (73). A cell-surface enzyme, neu­ sick building syndrome. Environ Health Eertpect 101: 234-238(1993) to a tissue. Histologically, inflammation tral endopeptidase (NEP), downregulates is characterized by edema, vasodilatation. neurogenic inflammation by degradating substance P. In the lung this enzyme is inhibited by cigarene smoke, viral infec­ tions, and toluene diisocynate, whereas Olfaction conicosteroids increase NEP. Cranial Nerve I ’ Neurogenic inflammation is now a Sensation of odor well-defined physiological mechanism by triggered by airborne which mediators are direcdy released from cbemicals sensory nerves to produce vasodilatation, edema, and other manifestations of in­ flammation. The nerve fibers have been identified as slow velocity C-fibers, and the regulation of neurogenic inflammation Common has been studied. Chemical Chemical Irritant Receptors ' Sense Cranial Nerve V The common chemical sense is a nasal Burning, irritation sensation provoked by airborne chemicals which is distinct from taste and smell triggered by airborne {14). This sense is experienced as a burn­ chemicals _ ing and painful sensation in the upper air­ ways and eyes upon exposure to irritant

Address correspondence to W. J. Meggs, Room Figure 1. Olfaction and the common chemical sense. Olfaction is the sensation of odor, transmitted by 4W54, Brody Building, Department of Emergency cranial nerve I, the olfactory nerve. The common chemical sense is a sensation of burning and irritation Medicine, East Carolina University School of in the airway, produced by irritant chemicals and transmitted by cranial nerve V, the trigeminal nerve. Metlidne, Greenville, NC 27858 USA.

234 Environmental Health Perspectives

CIT Y_2 IMC1 0 0_0"0 6 7 2 9 5 0 8

NYC-WTC_000199644