A comparison is made between the rectal and the body surface temperatures of fed mice housed in individual compartments without bedding while exposed continuously to environmental temperatures of 5° C, 15° C, and 25° C. Surface temperatures of the mice are related to the ambient temperature at which they are held. Rectal temperatures are known to undergo cyclic variations and, except for the first 24 hours at 5° C, are within normal limits throughout a week of exposure. Fasted animals at 5° C cannot maintain a core temperature beyond about 6 to 12 hours and all die within 24 hours. Injection of an LD50 dose of endotoxin fails to depress liver and muscle glycogen and total body carbohydrate after three hours at 15° C, but after an exposure of five hours liver glycogen alone remained unchanged. At 5° C, carbohydrate reserves were depleted in liver, muscle and total body after three hours in fasted mice but not in fed mice. After five hours, muscle glycogen alone was lowered. Endotoxin poisoned mice lost carbohydrates after three hours and five hours at both 5° C and 15° C.
Mice singly housed without bedding at 5° C clear carbon from the blood more slowly than animals similarly housed at 25° C. Increasing the time of exposure to cold to 2, 18 or 72 hours does not further alter the rate of clearance. Bacteria are also "cleared" uniformly at the two temperatures when a highly virulent strain (SR-11) of Salmonella typhimurium is injected intravenously, but not when one of low virulence (RIA) is used. The RIA strain disappears from blood more slowly in mice at 5° C than in those at 25° C. This was demonstrated both by dilution counts and by labeling the bacteria with p32 and following the decline in radioactivity of blood with time. Livers of mice were sampled at times postinfection for radioactivity and for viable bacterial counts. Housing temperature had no effect on radioactivity changes, but viable counts were higher and decreased more slowly in mice at 5° C than at 25° C. These findings are believed to account, in part, for the greater susceptibility to infection with RIA that was previously seen in mice exposed to cold compared to those at 25° C.
Mice housed at 25° C are protected by cortisone against endotoxin lethality when the hormone is given at the same time as the poison, but not an hour or two later. This is not true of mice housed at 5° C. Activity of liver tryptophan pyrrolase is lowered by endotoxin and elevated by cortisone only in animals at normal temperatures. When endotoxin and hormone are given concurrently, normal enzyme activity is maintained, but activity decreases when the hormone injection is given an hour or more after endotoxin. Actinomycin D, ethionine, 2-thiouracil, and 8-azaguanine (inhibitors of protein synthesis) when given in sublethal amount: potentiate endotoxin, prevent cortisone protection against endotoxin, and block the hormonal induction of tryptophan pyrrolase. Chloramphenicol has none of these effects. Mice infected with Salmonella typhimurium have lower than normal tryptophan pyrrolase activity and a smaller induction of enzyme by cortisone 18 hours postinfection than do normal mice or mice 42 hours postinfection. This occurs only at 25° C.
Mice made tolerant to bacterial endotoxin show an increase in rate of carbon clearance from the blood and a greater stability of liver tryptophan pyrrolase following endotoxin poisoning compared with normal mice. Injections of actinomycin D, but not of ethionine nor 2-thiouracil, prevent these changes associated with tolerance. Animals exposed to 5° C cold are capable of being made tolerant despite their increased sensitivity to endotoxin. Acclimatization to cold reduces this sensitivity. Neither hemagglutinins against endotoxin coated erythrocytes nor bacterial agglutinins show any change of titer in tolerant animals. It is believed that the phenomenon of tolerance is dependent upon enzymatic stabilization.