Effect of pituitary adrenocorticotropic and growth hormones on the resistance of rats infected with Pasteurella pestis.

The influence of highly purified pituitary adrenocorticotropic (ACTH) and growth (somatotropic, STH) hormones on resistance of normal, young adult rats infected with Pasteurella pestis organisms (EV 76) has been studied. The daily dosage of ACTH was 0.1 mg. (25 I.U per mg.) and that of STH was 1.0 mg. When these hormones were administered for 3 days prior to infection (1 LD(50)) and for 4 days thereafter, ACTH treatment resulted in a significant depression of resistance (p = < 0.001). The simultaneous administration of STH not only resulted in a definite counteraction of the depression (p = < 0.001), but resistance was increased to a level significantly above that of the non-hormone treated controls (p = < 0.001). Treatment with STH alone also showed a significantly higher protection when compared to the same controls (p = < 0.05). The results of experiments in which the challenge dose was 1 LD(50) suggested that greater alterations in resistance, whether it be a depression or enhancement, could be obtained by continuing hormone treatment after challenge instead of discontinuing on the day prior to challenge. When animals were treated with a relatively high daily dose (1.0 mg.) of ACTH and challenged with only (1/4) of an LD(50) of organisms, the majority of animals died within 4 to 7 days, whereas either the ACTH treatment or the bacterial dose alone resulted in no deaths. If the hormones were administered for 2 weeks prior to challenge with a high, toxic dose of organisms (4 LD(50)), and discontinued thereafter, there were significant differences in mortality in the various groups during the first 24 hours post challenge. The ACTH treated group showed a marked drop in resistance (p = < 0.001). STH, when given alone, exercised a significant protection (p = < 0.02), and in combination with ACTH, effectively counteracted the depression of resistance to acute, toxic deaths induced by the latter hormone (p = < 0.001). In this particular experiment, practically all animals died within 4 to 5 days, owing to the high challenge dose; the few survivors were in the group that had been pretreated with growth hormone. The maximal loss in body weight following an LD(50) challenge dose occurred by the 3rd day post challenge in all groups except in the ACTH-treated animals. At this time the LD(50) control group had lost an average of 14 gm. per rat, the STH group only 3 gm. per rat, whereas the group receiving both hormones lost an average of 7.5 gm. per rat. The ACTH-treated animals showed the greatest weight loss on the 4th day. Thus, under the conditions of the experiment, the beneficial effect of STH on the maintenance of body weight was demonstrated during the period of acute infection. The peak incidence of death in controls or hormone-treated animals following infection with 1 LD(50) of living organisms occurred on the 4th to 5th day post challenge; the earliest deaths occurred on the 3rd day, while the latest occurred on the 7th day. The peak incidence of death after the 4 LD(50) challenge dose occurred earlier, falling on the 2nd to 3rd day. Death was always accompanied by the characteristic gross pathology which results from infection with Pasteurella pestis organisms, particularly in the animals which succumbed after the 3rd day. Bacterial cultures usually revealed the presence of numerous Pasteurella pestis organisms in the spleen and heart blood at the time of death.