The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 94, 139-170, Copyright, 1951, by The Rockefeller Institute for Medical Research New York


ARTICLE

THE MECHANISM OF ACTION OF 17-HYDROXY-11-DEHYDROCORTICOSTERONE (COMPOUND E) AND OF THE ADRENOCORTICOTROPIC HORMONE IN EXPERIMENTAL HYPERSENSITIVITY IN RABBITS

Frederick G. Germuth Jr. M.D.1, Jiro Oyama 1, Barbara Ottinger 1, and With the Technical Assistance of Kenneth Q. Grow

1 From the Federal Security Agency, Public Health Service, National Institutes of Health, National Microbiological Institute, Laboratory of Infectious Diseases, Bethesda

The concurrent administration of compound E at a daily dosage of 2 mg. per kg. to rabbits receiving daily intracutaneous injections of crystalline egg albumin markedly inhibited the development of anaphylactic hypersensitivity of the Arthus type. ACTH, when given at a similar dosage, produced a much less marked effect. Both hormones suppressed circulating antibody and as with the Arthus reaction, the suppression produced by compound E was much greater than that obtained with ACTH.

When treatment with compound E was started following sensitization, there was a rapid decline in circulating antibody and, if the pretreatment serum antibody was low, there was also a progressive decrease in skin reactivity, becoming negative after 5 days of treatment. When the pretreatment serum antibody concentration was great, so that by the termination of treatment the antibody concentration was still above the level ordinarily sufficient for a maximal skin response, the Arthus reaction was unaffected by treatment.

These considerations as well as the failure of compound E to inhibit the systemic passive Arthus reaction suggest that the inhibitory effect of compound E and ACTH on the development of experimental hypersensitivity results from the hormonal reduction of circulating antibody.

Treatment with compound E had no effect on the rate of disappearance of circulating antibody in the passively immunized rabbit. This finding suggests that ACTH and compound E reduce circulating antibody by inhibiting antibody formation rather than by promoting antibody destruction.

The question is raised as to whether the marked lymphoid atrophy produced by these hormones may be related to the interference with antibody production.

Submitted on April 22, 1951


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