Medical Aspects of Chemical Warfare (2008) - The Black Vault

Toxic Inhalational Injury and Toxic Industrial ChemicalsTABLE 10-5Main Inflammatory Agents Involved in Acute Lung Injury, Their Source and ActionAgent source actionsCytokines (Proteins)IL-1 in response to infection/injury Regulates systemic inflammatory response, causesfrom activated macrophage. increase in blood neutrophils; causes fever. Inducesinduced by TNF fromother cytokines. Stimulates NO production, producesmononuclear and endothelial PLA 2, PAF, releases histamine.cells.IL-6 induced by IL-1 from epithelial Creates pyrogen, activates stromal bone marrow tocells.produce CSF.IL-8 Secreted by macrophages, Chemotactic for neutrophils and activates macrophages.endothelial cells, T cells andfibroblasts in response to LPS,il-1 or TNF stimulation.TNF-α Large amounts from endotoxin- Induces arachidonic metabolites and synthesis of cytokstimulatedmacrophages. ines. Chemotactic for neutrophils and macrophages.Synergistic with IL-1. Causes fever.Lipids (Arachidonic Acid Metabolites)Leukotrienes (B 4, C 4, D 4, E 4) Enzymatic pathway from Causes vasoconstriction, bronchoconstriction, enhancemembranephospholipid. ment of capillary leakage.Prostaglandin E 2Enzymatic pathway from A vasodilator, has proinflammaotry and antiinflammamembranephospholipid. tory potential.Thromboxane A 2enzymatic pathway from Potent vasodilator, causes platelet sequestration.membrane phospholipid.PAf epithelial cells via the causes platelet aggregation. Recruits eosinophils, causesarachidonic acid pathway, also vasodilation, increases vascular permeability, causesneutrophils, basophils and degranulation of neutrophils. Spasmogenic on bronchialplatelets.smooth muscle.Reduced Oxygen Species (Free Radicals)OH, H 2O 2, superoxide anion LPS stimulated macrophage/monocyte cell.Very reactive, responsible for lung tissue injury. Interactswith arachidonic acid pathway to increase levels ofeicosanoids.CSF: colony-stimulating factorH 2O 2: hydrogen peroxideIL: interleukinLPS: lipopolysaccharideNO: nitric oxideOH: hydroxyl radicalPAF: platelet-aggregating factorPLA 2: phospholypase A2TNF: tumor necrosis factorfactor-α may aid in fluid clearance in this injury model.The nature of lung injury in response to an inhalationalevent can be extremely complex. Figure 10-3 providesa visual representation of the alveolar region of the peripherallung compartment following exposure to toxicgas. The difficulty in treating an injury with a large arrayof metabolic chaos is that many of these pathwaysare activated and on-going simultaneously.Biochemical ResponsesUnderstanding the biochemical responses to inha-351