Delayed effects of stress and immune activation

Stress responses play a crucial adaptive role but impose potentially subversive demands on the organism. The same holds for the symptoms of illness as seen after immune activation by pathogens or tissue damage. The responses to immune stimuli and stressors show remarkable similarities and rely on similar control mechanisms in the brain: i.e. they involve neuropeptides of the corticotropin releasing factor (CRF) family. Immune and non-immune challenges lead to responses that normally show a temporal relationship with the duration and intensity of the stimulus and the (re)activity of the stress-responsive systems return to their pre-challenged state within hours or days. However, exposure of animals or man to specific stimuli can induce delayed and long-lasting (weeks, months) alterations in stress responsive systems, resulting in a prolonged period of increased stress vulnerability. Immune stimuli are particularly powerful in eliciting such a stress vulnerable state. Various adaptive changes in the (neuro)biological substrate as seen during this stress vulnerable state also occur in depression, and may be causally related to the depressive symptoms that are often associated with infectious and inflammatory diseases.