Immune activation and psychoneurogenic stress modulate corticosterone-releasing effects of lymphokines and ACTH

Possible modulatory effects of psychoneurogenic stress and endotoxin-induced immune activation on the in vitro corticosterone-releasing effects of lymphokine-containing supernatants (LCS) and adrenocorticotropic hormone (ACTH) were studied in rats. We have found that activation of the immune system by endotoxin increases the in vitro sensitivity of the adrenocortical cells to LCS and ACTH. In addition, we found that psychoneurogenic stress not only produced an increase of in vitro adrenal sensitivity to ACTH, but it also enhanced the release of corticosterone after perfusion of LCS. A synergistic interaction between ACTH and LCS was observed in all experimental groups of animals studied. An increased adrenal sensitivity to LCS and ACTH after stress or immune activation might have a functional significance, since the adrenal cortex is a major site in the response of the organism to alterations in the homeostatic balance. On the other hand, the temporal pattern of in vitro corticosterone release after LCS was different in all groups under study compared with that observed after ACTH challenge. LCS elicited a more rapid corticosterone response that lasted for a shorter time than after giving ACTH. These latter results suggest that different mechanisms may underlie the effects of LCS and ACTH on adrenal corticosteroidogenesis. In conclusion, the present findings further reinforce the existence of possible physiologically relevant interactions between the immune system and the pituitary-adrenal axis.