The Effect on mortality of 11-dehydro-17-hydroxy corticosterone and adrenocorticotropic hormones on secondary shock following thermal burns in mice.

The results of this investigation indicate that ablation of the adrenal cortex markedly increased susceptibility to lethal effects of thermal burns. On the other hand it was not possible to restore the degree of protection found to intact animal by administration of any of a wide series of graded doses of cortisone acetate to adrenalectomized burned animals. The most impressive results were found in that group of adrenalectomized animals given 0.05 mg./day of cortisone. This dose which protects 50% of the animals was for more effective than were larger or smaller amounts. Kumagai in his investigations showed that this dose maintained the lymphatic tissue, blood lymphocytes, and eosinophil count to be approximately that amount of hormone which maintains physiological conditions in the adrenalectomized animal. These findings were extended by Kumagai and confirmed. In subsequent experiments using CBA mice, the mice were treated in the same manner as previously described for adrenalectomized burned animals. First of all, it was found that the amount of burned surface had to be increased two-fold in order to produce 80% death in intact mice of the same age, sex and weight as compared to the adrenalectomized animals in the previous experiment. The exact area of eh burn was 692 mm2. The same series of graded doses of cortisone acetate (from 0.25 to 0.5 mg. per 20 gram mouse) was given. These doses were also given immediately after application of the burn. The results showed, surprisingly enough, that the 0.5 mg. dose produces approximately the same degree of protection in intact burned animals as that found in adrenalectomized burned mice (50%). None of the other dosages of hormone provided a significant degree of protection in the intact animals. The larger doses actually enhanced the rate of kill to such an extent that it exceeded that found in the non-treated control group. In view of the large number of animals used and the consistency of the results of various experiments, it is apparent that adrenalectomy approximately doubled the susceptibility of mice to thermal burns and that the optimum dosage to restore and degree of protection in the intact as well as adrenalectomized mice it tat amount which according to numerous other experiments is apparently a physiological dose. These results indicate from the practical point of view, treatment of burned individuals with other than an optimal dosage of cortisone could have serious consequences. The same procedure as that outlined above was followed in another series of experiments in which intact female mice of the CBA strain were subjected to an amount of burned surface which produced 80% death in non-hormone treated animals. Graded doses of ACTH, from 0.025 mg. to 0.5 mg. were given immediately after application of the burn. The only dose which provided any degree of protection was the 0.25 mg dose. Larger doses of ACTH, as with the case with cortisone, produced a rate of kill greater than that found in the untreated control group. The question as to whether pre-treatment with cortisone might lower the rate of mortality was also considered. On the basis of other experiments, it was found that cortisone could be sorted in the tissue and be available for protection of the animal following stress. We assumed that similar results might be obtained when thermal burns were the stressing agent. CBA mice were adrenalectomized and give graded doses (0.25 mg. to 0.2 mg.) of cortisone daily for six days. The animals were then burned on the seventh day allowing a 24 hour lapse between the last injection and the time of burning. No protection against the lethal effects of the burns was found among any of the animals given any of the five graded doses of cortisone acetate. Thus the results of this experiment indicate that unlike protection against anaphylactic shock and histamine administration, pre-treatment with cortisone had not effect on the rate of kill. Histological studies show that the cells in the inflammatory area immediately after burning the surface of the skin, are predominately eosinophils. Unlike the early stages of inflammation produced by most phlogogenic agents, invading cell per mm2 of tissue indicated that the greater the cortisone dosage the fewer the eosinophils in the burned area.