Long-term consequences of social stress on corticosterone and IL-1beta levels in endotoxin-challenged rats.

Social stress has strong and long-lasting effects on autonomic nervous, neuroendocrine and behavioural functioning. The functionality of the immune system is profoundly influenced by autonomic nervous and neuroendocrine activities. Changes in sympathetic-adrenal and hypothalamic-pituitary-adrenocortical (HPA) axis activities as observed during and after social defeat, therefore, probably represent an important factor in the modulation of the immune response. In the present study, the impact of social defeat stress on the responsiveness of the immune system was studied by the presentation of a systemic inflammatory challenge through the injection of the bacterial endotoxin lipopolysaccharide (LPS). Male Wistar rats were subjected twice to social defeat 7 days apart. One week after the second defeat, they were injected with LPS in a low (150 microg/kg; D<LPS) or a high dose (375 microg/kg; D>LPS). Another group of defeated rats was injected with saline. Control, nondefeated rats also received the immune challenges. Previously defeated rats responded to the high dose of LPS with a deficient corticosterone (CORT) response resulting in an aggravated interleukin-1beta (IL-1beta) response 4 h after LPS injection. Furthermore, the experiments indicated that mortality rates after LPS administration were high in previously defeated rats, whereas mortality was absent in nondefeated rats. The results indicate that social stress has long-lasting effects on the functioning of the immune system and that it can seriously compromise the effectiveness of the adrenocortical response in containing some immunological defense mechanisms.