Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/5/1997
Publication Date: N/A
Citation: N/A Interpretive Summary: Severe illness results from even short term smoke inhalation associated with exposure to particulate and toxic combustion products of fires. Lung injury results, in part, from the localized over production of hormones from the immune cells called cytokines that go to the lung to scavenge and neutralize contaminants that are inhaled. In some forms of inhalation disease, a specific cytokine called tumor necrosis factor-alpha (TNF) is released locally in the lung and subsequently promotes the formation of other biologically active molecules that cause cells in the lung to die or cause general lung irritation. There is a need to identify which forms of inhalation toxicity are associated with increases in TNF. Likewise, there is a need to determine levels and durations of smoke exposure that cause increased TNF. release in the lung. This is important because there are many strategies that can be used to decrease TNF production locally (inhales steroids, etc) but it needs to be established (1) is TNF. is involved in a particular form of smoke distress and (2) if reducing TNF. release after smoke exposure is more beneficial or deleterious to the victim. We used a sheep model to test if exposure to smoke resulted in increased lymph content of this TNF cytokine . Further experiments will explore if certain regions of the lung are more or less sensitive to effects of smoke inhalation and suggest strategies to reduce the degree of lung problems associated with TNF.
Technical Abstract: Respiratory complications such as adult respiratory distress syndrome ( ARDS ), are major causes of morbidity and mortality in fire victims. The cytokine TNF is edematogenic and has been found to play a role in other forms of ARDS. We utilized the chronic cannulated, pulmonary lymph fistulated sheep as an animal model to examine the effects of graded doses of cotton smoke inhalation on the onset of ARDS and pulmonary TNF production. Smoke inhalation induced a rise in lymph flow and pulmonary artery pressure that was associated with no fall in plasma/lymph protein ratio (high smoke level) and a modest fall in the ratio at low dose smoke. Lymph concentrations of TNF declined in both smoke groups although lymph flux (concentration x flow) transiently increased in both sheep groups. In neither case sis lymph flux of TNF exceed that induced by left atrial pressure elevation which also transiently increased lymph flux of TNF. Thus, in sheep utilizing a sensitive and specific radioimmunoassay for TNF. we were unable to demonstrate a role for TNF in smoke-induced microvascular lung injury.