TNF and infection: Cytokines such as TNF-α link the non-specific immune system to the hypothalamo-pituitary-adrenocortical (HPA) axis: inflammatory cytokines — such as TNF-α and its soluble receptors p55 and p75 — released during infection and inflammation activate the HPA system at the hypothalamic, pituitary, and adrenal level resulting in the release of cortisol as the most important negative feedback signal to prevent an overshoot of the ongoing host defense [42, 89, 96]; glucocorticoids, in turn, suppress the production of pro-inflammatory cytokines.