Sex (always) matters: inflammatory, neuroendocrine, and psychological responses to endotoxin

Abstract

Depressed mood and increased anxiety represent core symptoms of sickness mediated by pro-inflammatory cytokines. Moreover, inflammation seems to be implicated in the development of mood disorders. Although women are known to mount stronger pro-inflammatory responses and are at higher risk to develop depressive/anxiety disorders, experimental studies on sex differences in sickness-related behavioral symptoms are scarce. Thus, we compared physiological and psychological responses to endotoxin administration in healthy men and women. Subjects were injected with lipopolysaccharide (LPS; 0.4 ng/kg) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until 6h after endotoxin administration. Women exhibited a more profound pro-inflammatory response (TNF-a, IL 6) and higher increases in anti-inflammatory IL-1ra. The LPS-induced increase in IL-10 was higher in men. Cytokine alterations were accompanied by changes in neuroendocrine factors involved in inflammation regulation. Endotoxin administration induced an increase in noradrenaline, without evidence for sex differences. Cortisol responses were significantly higher in woman. LPS administration also increased prolactin secretion, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing exaggerated sickness responses. Disturbance of these compensatory mechanisms may promote the development of affective disorders in women.