SECONDARY BACTERIAL INFECTION IN MICE 



time in mice at 25° C. Similarly, the titer of virus in the liver was 

 higher on the fourth day in mice at 49 C than in mice at 25° C. 

 These experiments indicate that although adult mice possess a 

 natural resistance to the Coxsackie virus such that the disease is 

 limited to a non- fatal infection, this resistance is lost when animals 

 are maintained in the cold. Under these conditions, a lethal infection 

 ensues which is characterized by a persisting viremia, high levels 

 of virus in the liver, and lesions demonstrable in other organs. The 

 mechanism by which cold reduces resistance to the virus is unknown, 

 although the fact that cortisone causes a similar loss of resistance 

 suggests that cold may act through its capacity to augment secretion 

 of adrenocortical steroids. It may also result in the involvement of 

 other body responses less well defined. Thus, Walker and Boring 

 (1958) observed that neutralizing antibody appeared on the fourth day 

 in mice at room temperature but failed to appear in animals in the 

 cold. Injections of cortisone are known to suppress the immune re- 

 sponse (Germuth, 1956), 



Schmidt and Rasmussen (1960) reported that mice maintained at 

 37° C were more resistant to infection with herpes simplex virus 

 than those held at 25° C. This protective effect was believed to be 

 due to the lower viral population in brain tissue at the higher tem- 

 perature. The mechanism responsible for this decrease in the num- 

 ber of viruses in unknown, but a possible explanation for the dif- 

 ference in mortality rates is an alteration in viral multiplication due 

 to a temperature induced change in the metabolism of host tissues. 

 It has been well established that viral populations can be controlled 

 to some extent by only a few degrees change in temperature 

 (Lwoff, 1959), 



The object of the present study was to determine possible dif- 

 ferences in the course of salmonellosis in mice maintained at 25° C 

 with others kept at 5° C, and to uncover, if possible, mechanisms 

 responsible for such differences. It was not our intention, however, 

 to employ mice with a controlled hypothermia. In the first place, the 

 lower environmental temperature to which animals were subjected 

 failed to depress the core temperature below the normal range. In 

 addition, to attempt to regulate the degree of hypothermia in popula- 

 tions of mice the size of those used in the experiments would have 

 been technically beyond the resources available. The ability of mice 



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