Inflammation may serve as one of the principle initiators of acute and chronic lung disease in man. Inflammatory hormones are transiently released into the blood at very low concentrations. Because of their extremely low concentration, lability and destruction within blood and surrounding tissues, detection and quantitation in vivo is difficult. Using isolated guinea pig lungs, the release and concentration of the inflammatory hormones, histamine, prostaglandins, bradykinin, slow reacting substance of anaphylaxis (SRS-A) and the concentration of free fatty acids will be determined by simultaneous assay using isotonic contractions of four different superfused muscle preparations and by chemical analysis. The muscle preparations will be sequentially superfused with oxygenated Tyrode's solution effluent from the lung containing specific antagonists to render the individual muscles sensitive to specific hormones, as in the method of Vane. Release of inflammatory hormones will be initiated in perfused lungs by ventilation with air containing oxidizing air pollutants (NO2 and O3), or organic vapors (carbon tetrachloride or dichlorethane), or with proteolytic agents (SO2 or aerosols of papain or ficin). Levels of exposure will correspond to industrial exposure. In other experiments, the perfusion fluid will be treated with biogenic amines, cholinergic and adrenergic agonist and antagonists, precursors and inhibitors of prostaglandin and bradykinin, non-steroid anti-inflammatory drugs, thiols and phenols, to determine mechanisms of release, inhibition and destruction by the lung. These studies will provide quantitative estimates of the extent and duration of the release of inflammatory hormones by the lung on inhalation exposure. They will provide insight into the role of the lung in both the release and destruction of these mediators of inflammatory response. These studies may lead to a better understanding of the potential role of inflammation in inhalation toxicology in man.
NIH ExPorter
NIH ExPorter