- - - - - 1 Pathogenesis of bacillary dysenter LICROFICHE Min laboratory animals

Abstract

PROGRESS IN CLARIFYING the disease process of bacillary served. Ulcerative lesions of the bowel not unlike those dysentery has been hampered by the lack of a convenient observed in the natural host are noted. The distribution annial with which to work, for man, the chimpanzee, of these lesions depends upon the time when the animal ' and the monkcy are the only natural hosts. The result is succumbs. If it dies within 48 hr after challenge, lesions * that after 6o-odd years of research, we do not have any of the small intestine predominate (Fig. I), whereas notion of how pathogenic dysentery bacilli differ from severe lesions of the cc Lim and colon are seen in those nonpathogenic Escherichia coli. Indeed, the fundamental animals dying at a later time (Fig. 2). The intestinal problem of defining the characteristics which endow the tract of starved animals fed heat-killed bacteria remains former with the capacity to cause dysentery while the normal. Similarly, the normal anatomical features of the latter passes through the bowel, usually without causing intestinal tract are preserved when living cultures of E. symptoms, has not been answered. We and others have coti or nonpathogenic strains of Shigellae are administered. attempted to study the infection in small laboratory Many factors, no doubt, are involved in rendering the animals in the hope that the findings obtained under starved guinea pig susceptible to the fatal enteric infecthese artificial conditions might give us some hints on the tion with dysentery bacilli. We have studied two of these disease process as it occurs in nature. Much of the in some detail. First, histologic examination of the major experimental work in the study of bacillary dysentery organs of starved guinea pigs revealed that the only has been carried out in mice infected by the intrapericonsistent change brought about by the starvation toneal rouce. However, an approach such as this is someprocedure '%as a centrilobular fatty degeneration of the what limited, for the factors influencing infection of the liver. This striking change led us to try a common peeitoneal cavity must necessarily differ from those chemical, hepatotoxin, in an attempt to reproduce the operating in the intestinal tract. same pathological changes. It was found that a subWhile normal guinea pigs exhibit little or no reaction cutaneous injection of a sublethal dose of carbon tetraafter oral administration of virulent dysentery bacilli chloride could substitute for the starvation period. If one followed by an intraperitoneal injection of opium, gave a small dose of carbon tetrachloride, 24-48 hr prior animals which have been deprived of food for 4 days to oral challenge with dysentery bacilli, the pattern of usually die after being fed the bacteria, providing a drug death and pathological changes in the intestinal tract such as opium is injected (7). It is this experimental were the same as those seen in animals which had been model, the infected starved guinea pig, which we should starved (8). like to characterize and try to relate the findings obThese experiments suggested that a physiologic lesion tained from it to the natural infection. First, the model of the liver played a role in the over-all reaction of the infection is specific in the sense that animals die followanimal to the experimental infection. The liver has long ing oral challenge with I X 0 o Shigella flexneri but surbeen considered an organ of detoxification, and the revive the feeding of even higher doses of E. coli strains isosults of toxicity experiments, summarized in Table 3, lated _rom healthy human beings (Table I). In addition, demonstrate that both starved and carbon tetrachlorideliving dysentery bacilli are required to cause a fatal intreated animals are much more susceptible than normal fection: animals survive the oral administration of io" animals to bacterial endotoxin, the only known toxic dead cells but succumb when io7 living bacteria are product of S. flexnri (9). The lesion of the liver must be administered per os (Table 2). somewhat specific in that the administration of allyl Death usually occurs 24-48 hr after the challenge alcohol, which also causes severe changes in the liver, strain is fed but can take place as long as a week later. does not appreciably increase the animmals susceptibility Diarrhea is not seen in ani%,.als dying within 48 hr of to endotoxin (WV. E. Farrar, Jr., personal communicachallenge but is common in the relatively few animals tion). Others have demonstrated that liver extracts have that succumb later in the disease process. The infection the capacity to inactivate endotoxin in vitro and that the is limited to the bowel; bacteremia has not been obinactivation process appears V ICYe tic in nature ICopies NOT available to DDC o lg1ioa Btolmr. APR 9 196

2 Figures and Tables

Cite this paper

@inproceedings{LABREC, title={- - - - - 1 Pathogenesis of bacillary dysenter LICROFICHE Min laboratory animals}, author={H . LABREC and H. Schneider} }