ACTH‐dependent modulation of malaria immunity in mice

Abstract

Tetracosactrin, a synthetic adrenocorticotrophic hormone (ACTH) analogue delivered by osmotic minipumps implanted s.c. in mice induced a dose-dependent increase of plasma corticosterone levels. In mice with an established immunity to Plasmodium berghei the increase of the plasma corticosterone level due to tetracosactrin treatment correlated with loss of immunity against this malaria parasite. The observed plasma corticosterone levels associated with loss of malaria immunity were of the same order as those in mice that lost their immunity during pregnancy. Adrenalectomy before administration of the ACTH analogue prevented both the increase of plasma corticosterone and loss of malaria immunity. Adrenalectomized mice still lost their malaria immunity when treated with the synthetic corticoid dexamethasone. The effector function of malaria immunity is sensitive to corticoids, and, at least during pregnancy, the naturally occurring serum corticosterone level appears to be an important regulator of malaria immunity.

Adrenal hormones mediate disease tolerance in malaria

“…Despite the established findings of increased GC levels in patients infected with malaria, their functional role has received no recent attention. Studies in the 1980s concluded that in immunized mice, pregnancy-associated increases in corticosterone levels cause the loss of malarial immunity and more recrudescences 16 – 18 . An earlier and limited study reported that adrenalectomy reduced survival of NMRI mice after P. berghei K173-infection, though the mechanism was not explored 19 .…”