PLATES 6 AND 7(Received for publication, July 29, 1963) Inhaled bacteria disappear rapidly from the lungs of experimental animals (1-3). This early clearance of bacteria is thought to be an important process in non-specific resistance to infection in the bronchopulmonary tree. Quantitative methods of study have provided a sensitive tool for detecting small as well as large changes in the efficiency of these mechanisms of resistance. A wide variety of chemical, hormonal, and environmental agents depress, :to different degrees, the rate at which inhaled cultivable bacteria disappear from the lungs (4). Such studies support epidemiologic evidence that multiple agents may be involved in the pathogenesis of chronic infections It is not clear to what extent each of the several component defense systems of the bronchopulmonary tree participates in the initial inactivation of inhaled bacteria. Although the mucociliary stream is frequently credited with this cleansing action, indirect evidence suggests that bacterial clearance may be accomplished by alveolar macrophages. In an attempt to answer this question directly, the pathway through the lung followed by inhaled bacteria was first traced by bacterial localization studies using conventional histologic and immunofluorescence methods. The latter method was used to localize bacterial antigen where the structural integrity of the organism had been destroyed. Then, radio-labeled viable bacteria were used to compare the rate at which inhaled bacteria lose their viability with the rate at which they are physically removed from lung tissue. In this way the action of bactericidal mechanisms such as phagocytosis was compared with the action of removal mechanisms such as the mucociliary stream and lymphatic drainage. The results of both studies point to the phagocytic action of macrophages as the major mechanism of early resistance to bacterial infection.

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Although much quantitative information has been accumulated on the properties of mechanisms of defense against systemic bacterial infection, relatively little parallel information exists for the defensive mechanisms of the respiratory tract. Yet, the bronchi and the pulmonary parenchyma are able to maintain a sterile environment despite virtually continuous exposure to inhaled bacteria.Lurie, Heppleston, Abramson, and Swartz (1) and Middlebrook (2) adapted aerosol techniques developed by Wells (3) to quantitative studies of experimental pulmonary infection with tubercle bacilli. \Vith similar techniques, Laurenzi, Berman, First, and Kass (4) have defined quantitatively the antibacterial action of the lungs of mice against inhaled staphylococci and have shown that within a few hours most of the retained bacteria can no longer be cultured. The precise mechanisms by which the rapid pulmonary defensive response occurs are not clear. As a first approach toward understanding these mechanisms the effects of certain agents on pulmonary clearance of bacteria were studied.Because of suggested clinical associations between decreased host resistance and alcoholic intoxication, hypoxia, corticosteroids, and starvation, these agents were selected for study. It would be expected that agents associated with increased susceptibility to infection would impair pulmonary bacterial clearing if, indeed, this action * Submitted for publication July 15, 1963; accepted October 11, 1963. MethodsThe methods used to produce pulmonary infection were essentially those of Laurenzi and associates (4). White Swiss mice of either sex were exposed to a finely divided aerosol of a suspension of Staphylococcus aureus (FDA 209P, type 42D) in phosphate buffer. After exposure half of the animals were killed immediately and the remainder 4 hours later, and the lungs were removed and cultured quantitatively. The clearance activity of the lungs was assessed by comparing the total numbers of bacteria present in the lungs immediately after exposure with the total numbers present 4 hours later. This clearance activity was measured first in untreated animals from the colony and then in groups of animals exposed to ethanol intoxication, hypoxia, starvation, or injection of corticosteroid.The animals were grouped according to the treatment received. In the animals that were intoxicated with ethanol, 3 ml of 5% ethanol in water was injected intraperitoneally 15 to 30 minutes before exposure to the aerosol. Hypoxia was induced in a decompression chamber in which atmospheric pressure was reduced by 380 mm Hg. Ventilation of the chamber was achieved by continuous flow of room air at a rate of 5 to 6 L per minute through the chamber. Steroid-treated animals were injected subcutaneously with 10 mg of cortisone acetate 24 and again 2 hours before exposure to the aerosol, with the intention that only the acute effects of massive doses would be studied. The starved animals were deprived of food, but allowed water at will for 24 to 48 hours before infection. \Veig...