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Four patients treated with depot tetracosactrin for 10 to 18 months maintained normal hypothalamic-pituitary-adrenal function assessed by the nyctohemeral variation of plasma corticosteroids and by the responses of plasma corticosteroids to insulin-induced hypoglycaemia, lysine-vasopressin, and depot tetracosactrin. The pituitary component of the response was analysed by measuring plasma immunoreactive ACTH levels. Three patients showed a nyctohemeral ACTH rhythm and normal ACTH responses to insulin-induced hypoglycaemia. Consistently undetectable morning plasma ACTH levels were found in the fourth patient, who also showed an unusually delayed rise in both ACTH and corticosteroid levels in response to insulin-induced hypoglycaemia, though the peak values attained were normal.The lack of suppression of hypothalamic-pituitary-adrenal function together with the good clinical response in these four patients suggests that treatment with depot tetracosactrin should be considered when long-term corticosteroid therapy is required.

The effect of antigenic competition on various parameters of humoral antibody formation and cellular immunity was studied in mice. Several pairs of antigens were employed in the investigation of the competitive aspects of induction of humoral antibody formation. Induction of a primary immune response to hemocyanin in Swiss white female mice moderately suppressed the induction of both 19S and 7S antibody formation to goose or rat erythrocytes. Suppression of 7S antibody formation was maximal when a time interval of 1-3 days separated the sequence of injections, although suppression was noted for intervals of up to 14 days. The induction of a primary immune response to rat RBC, the second of the two antigens in sequence, also suppressed The induction of both 19S and 7S antibody formation to goose RBC when appropriate intervals of 1-3 days were employed between injections. The induction of a secondary immune response to rat RBC totally suppressed the primary induction of both 19S and 7S antibody formation to goose RBC administered in the appropriate time sequence. Subsequently, it was shown that the secondary immune response to the suppressed antigen (goose RBC) elicited 30 days after induction of a primary immune response (5 days after secondary immunization with rat RBC) was characterized by deficient 19S and 7S antibody production. These levels were suppressed even in comparison with a normal primary immune response to this antigen. The results were interpreted in part on the basis of a deficiency of formation of primed cells associated with immunological memory. Alternatively, evidence was obtained for the development of a split type of immunological tolerance in 6 of 10 animals studied, since a total suppression of 7S antibody production was obtained in association with deficient 19S antibody synthesis (titers < 1/10). The induction of a primary immune response to several antigens in A/J female mice suppressed the processes of cellular immunity as manifested by prolonged survival of skin grafts from C57 BL/6J female donors. These results were interpreted as evidence for the existence and utilization of processing cells by the initial immune stimulus yielding a deficiency of cells available for processing the second antigen administered in sequence.