PREVITE AND BERRY 



response to endotoxin is prompt and dramatic (Conti et al., 1961; 

 Berry and Smythe, 1961), The period of sensitization to lipopoly- 

 saccharice by cold exposure (Tables Vaand Vb) is paralleled by the 

 time at which a drop in body temperature occurs following cold 

 exposure and/or endotoxin poisoning (Table VI). Whether the re- 

 duction in rectal temperatures is the cause or result or merely re- 

 flects metabolic changes that account for sensitization remains 

 unanswered. However, the latter view seems more likely in view 

 of recently obtained but yet unpublished data from this laboratory. 



Sensitization of mice to bacterial endotoxinby cold exposure may 

 be related to adrenocortical function. Ifthe stress of cold results in 

 an initial h3T)eractivity of the gland, an alarm reaction would occur 

 as part of a general adaptation syndrome (Selye, 19 55). Adrenal 

 activity is said to leveloff after an initial rise following exposure to 

 cold (Heroux and Hart, 1954a; Schonbaum, 1960), while the low 

 cholesterol content of the adrenals of room temperature exposed 

 mice 17 hours after endotoxin administration has been interpreted as 

 being the result of an earlier hyperactivity of these glands (Berry 

 and Smythe, 1961). In view ofthe protection cortical hormones afford 

 against endotoxin (Br ookeetal., 19 59), cold stress (Heroux and Hart, 

 1954b), or both of these factors combined (Table VII), the following 

 postulate does not seem unreasonable. The greater resistance to 

 endotoxin of cold- acclimatized mice compared to non- acclimatized 

 animals may involve a greater capacity ofthe adrenal ofthe former 

 to release protective corticoids at the proper time. In rats exposed 

 to 5° C, the maximal activity ofthe adrenal cortex as shown by P^^ 

 uptake occurs at 2 hours after exposure (Rossiter and Nicholls, 

 1957), Thus it may be than an initial depletion of corticoid reserves 

 occurs in the cold exposed mouse prior to the time at which these 

 hormones are needed for protection against endotoxin. "Functional 

 adrenalectomy" due to temperature stress, therefore, maybe re- 

 sponsible for sensitization of cold exposed mice to endotoxin, just as 

 surgical adrenalectomy has been reported to do so in rats (Brooke 

 et al., 1959). 



While the present report emphasizes adrenal cortical involvement 

 in protection or sensitization to endotoxin following cold exposure, it 

 is our opinion that more data must be gathered concerning other 

 facets of endocrine involvement, metabolism, and host defense 



230 



