Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms

Brain Behav Immun. 2016 Feb:52:18-26. doi: 10.1016/j.bbi.2015.08.013. Epub 2015 Aug 17.


Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, 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 or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness response. Disturbance of these compensatory mechanisms by environmental factors such as stress may promote the development of affective disorders in women.

Keywords: Anxiety; Cytokine; Endocrine; Endotoxin; Gender; Inflammation; Lipopolysaccharide; Mood; Sex; Sickness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects
  • Cytokines / blood
  • Cytokines / immunology
  • Emotions / drug effects
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / immunology
  • Illness Behavior / drug effects*
  • Illness Behavior / physiology*
  • Inflammation / blood
  • Inflammation / chemically induced
  • Inflammation / immunology*
  • Inflammation / psychology*
  • Lipopolysaccharides / administration & dosage*
  • Lipopolysaccharides / blood
  • Male
  • Neurosecretory Systems / drug effects*
  • Severity of Illness Index
  • Sex Factors
  • Surveys and Questionnaires


  • Cytokines
  • Lipopolysaccharides
  • Hydrocortisone