Stress and cytokine-elicited neuroendocrine and neurotransmitter sensitization: implications for depressive illness.
Stressful events, by their effects on neurotransmitter and neuroendocrine processes, are thought to favor the development or exacerbation of depressive illness. In as much as immunological challenge, may provoke stressor-like neuroendocrine and central neurochemical changes, the view was offered that immune activation essentially acts like a stressor and may contribute to the evolution of affective illness. In this respect, viral and bacterial infections appear to influence behavioral/metabolic (e.g. fever, anorexia, somnolence) and neurotransmitter functioning through the release of cytokines, which act as messengers between the immune system and brain. The present report provides a brief overview of the neurochemical consequences of proinflammatory cytokine treatments, particularly the actions of interleukin (IL)-1beta and tumor necrosis factor-alpha. As well, synergy with psychogenic and neurogenic stressors are described, as are data showing that cytokines, like stressors, may have time-dependent proactive (sensitization) effects, so that reexposure to the treatments greatly augments hypothalamic-pituitary-adrenal activity, as well as central neurochemical changes. Indeed, the neurotransmitter alterations are not restricted to hypothalamic nuclei, but occur in several extrahypothalamic sites, including various limbic regions. It is suggested that by virtue of these neurochemical changes, cytokines may have both immediate and proactive effects on mood states.
Hayley
Shawn
S
Institute of Neuroscience, Carleton University, Canada. shawnhayley@sympatico.ca
Merali
Zul
Z
Anisman
Hymie
H
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003866:Depressive Disorder / Q000503:physiopathology; D006801:Humans; D009490:Neurosecretory Systems / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D013312:Stress, Physiological / Q000503:physiopathology*
D016207:Cytokines; D018377:Neurotransmitter Agents