Age and sex steroid-related changes in glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress.

Aging is associated with an increased susceptibility to infections and chronic inflammatory diseases. This might be caused by dysregulations of the endocrine system with increased activity of the hypothalamus-pituitary-adrenal (HPA) axis and decreased levels of sex steroids. Therefore, we investigated the stress-response of the HPA axis and glucocorticoid (GC) sensitivity of pro-inflammatory cytokine production in elderly men, compared to testosterone-treated elderly men and young controls. Stress-induced increases in cortisol did not differ significantly between experimental groups (F=2.10; p>0.10), but GC sensitivity increased significantly in young controls and testosterone-treated elderly men, while a decrease was found in untreated elderly men (F=5.28; p<0.01). We conclude that the increase in GC sensitivity after stress serves to protect the individual from detrimental increases of pro-inflammatory cytokines, a mechanism that is disturbed in elderly men and partly restored by testosterone treatment.