Evidence of vascular injury was found in rabbits after a single small dose of endotoxin from Escherichia coli. Eighty percent of the treated animals developed circulating endothelial cells, leukopenia, and thrombocytopenia, and 50 percent had aortic endothelial lesions as determined by electron microscopy. Prior anticoagulation with heparin did not prevent this response. No control animals showed these abnormalities.

It is well recognized that representatives of three bacterial genera, Staphylococcus, Streptococcus, and Hemopkilus, which are frequently present in the upper respiratory tract of man, have only a limited capacity to produce a primary pneumonia in adults. When pneumonia induced by one of these microorganisms does develop in an adult, it arises almost invariably in association with influenza virus infection or preexisting morphologic abnormalities of the bronchopulmonary structures. This situation is quite unlike that seen with Pneumococcus which has the capacity to initiate a primary pneumonia in the absence of influenza viral infection.The mechanism by which influenza influences staphylococcal, streptococcal, or influenza bacillus pneumonia has been the subject of relatively few studies in laboratory animals in the 28 years that have elapsed since the first isolation of influenza virus. Human studies have usually not employed the methods of quantitative bacteriology and have been complicated by the widespread use of antimicrobial agents.In 1941, Glover (1) noted the spontaneous occurrence of Group C streptococcal pneumonia in ferrets infected with influenza A virus. He demonstrated the increased * This investigation was supported, in part, by research grants E-635 and E-1595 from the National Institute of Allergy and Infectious Diseases, Public Health Service; and by grants from the Pfizer Foundation; from the Committee on Medical Research of the American Tmdeau Society, medical section of the National Tuberculosis Association, with assistance from the Iowa Tuberculosis and Health Association and the Greater Hartford Tuberculosis and Public Health Society. 238INFLUENZA VIRUS pathogenicity of this combination and the inability of streptococci to induce the disease in the absence of the viral infection. Later, Francis and DeTorregrosa (2) found that strains of H. influenzae produced extensive lethal pneumonia in mice previously infected with influenza virus. It was necessary for influenza virus infection to precede the introduction of bacteria; simultaneous inoculation of the two agents or of H. influenzae alone resulted in no bacterial disease. Similar results were noted with strains of beta hemolytic streptococci. Carlisle and Hudson (3,4), also demonstrated the synergism of a combination of beta hemolytic streptococci and influenza A virus.Harford and others (5) observed that pneumococci introduced intrabronchially were cleared from the normal mouse lung with great efficiency. Even when influenza virus had been present 24 hours and multiplication of virus had begun, disappearance of the pneumococci was not impeded. When pneumococci were introduced after 5 days of influenza, however, they multiplied and produced extensive disease. This suggested the operation of some factor concerned with the influenza viral lesion which did not appear until after more than 24 hours of viral infection. Harford considered this factor to be pulmonary edema fluid and has reported a number of experiments which support this concept...

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