STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA : I. THE ACTION OF TYPE SPECIFIC ANTIBODY UPON THE PULMONARY LESION OF EXPERIMENTAL PNEUMONIA.
A uniformly fatal lobar pneumonia was produced in white rats by inoculation of the left main bronchus with virulent Type I pneumococci suspended in mucin. All of the animals succumbed in less than 5 days, half of them dying within 48 hours. In only 5 of 40 rats was the lesion confined to the left lung, and all but one developed pleurisy, pericarditis, or both. All had bacteriemia at the time of death. The pathogenesis of the pulmonary lesion was studied by examining the lungs of 35 rats killed at various intervals following inoculation. The pneumonic process spread rapidly until most of the left lung was involved in 36 hours. Frequent blood cultures showed invasion of the blood stream in a few rats at 6 hours and in over 90 per cent at the end of the first day. The first signs of pleurisy usually appeared at 18 hours. Microscopic examination of the actively spreading lesion revealed three characteristic zones: (1) an outer "edema zone" in which the alveoli contained many pneumococci floating freely in edema fluid, (2) a middle zone where both leucocytes and organisms were present, many of the latter being phagocytized, and (3) an inner zone of advanced consolidation in which the alveoli contained many leucocytes but no organisms and where there were already local areas of early resolution. Study of numerous lesions, at intervals of from 12 to 36 hours after inoculation, indicated that the pneumococci spread into normal alveoli principally by way of the infected edema fluid in the outer zone. Pneumococcus-laden edema fluid in large bronchi and in alveoli beneath the pleura suggested the mode of spread of the infection to other lobes and possibly to the pleural cavity. No adequate explanation could be found for the presence of active phagocytosis in the lungs of animals with bacteriemia and presumably without circulating antibodies, but this conspicuous phagocytic reaction was obviously responsible for the clearing of the central part of the spreading lesion. The action of type specific antibody upon the pulmonary lesion of experimental lobar pneumonia was studied in rats similarly infected but treated with antipneumococcal serum. When injected intravenously in a single dose within 18 hours after inoculation the antiserum was found to protect all of the rats against the otherwise fatal pneumonia. It stopped the spread of the pneumonic lesion, cleared the blood stream of organisms, and prevented the extension of early pleurisy. The antibody caused agglutination and capsular swelling of the pneumococci in the lung, particularly in the edema zone at the margin of the lesion where they were most numerous. Apparently immobilized by agglutination the organisms were overtaken by leucocytes and destroyed by phagocytosis. The phagocytic reaction was greatly accelerated by the specific opsonins of the antiserum, and the pneumococci were destroyed by polymorphonuclear leucocytes before many macrophages appeared in the alveolar exudate. Within a week after treatment resolution of the pulmonary lesion was well in progress. Both horse and rabbit antibody were shown to penetrate the lung, and immune bodies were demonstrated in the alveoli within 10 minutes after the start of treatment. The relation of the observed phenomena to the curative action of anti-pneumococcal serum has been briefly discussed, and it is pointed out that the principal effect of antiserum is to cause immobilization of the pneumococci in the advancing edema zone. Experiments to be reported in a later publication have shown that sulfapyridine exerts a similar effect through a different mechanism.
Department of Bacteriology and Immunology, The Harvard Medical School, Boston.
W B
WB
Wood