Department of Adult Psychiatry University of Medical Sciences in Poznan Szpitalna 27/33,60-572 Poznan, Poland
An interaction of genetic factors with environmental factors, including stress and infectious agents, is assumed to play a causal role in the pathogenesis of major depression. Since the rate of major depression in genetically succeptible populations has continued to increase over the past years, the identification of these environmental factors would provide targets for more effective antidepressant agents.
There is now evidence that cytokines, peptide hormons, and neurotransmitters, as well as their receptors, are endogenous to the brain, endocrine, and immune systems (Blalok, 1994). These shared ligands and receptors provide common chemical language for communication within and between the immune and neuroendocrine systems. This organization of communication suggests an immunoregulatory role of the brain and a sensory function for the immune system. Accordingly, the immune system, may be viewed as a sensory organ that recognizes physical and emotional stress (trauma) and relays this information to the CNS and endocrine system via the cytokines.
The existence of dysregulations of the stress response in depression could potentially reflect a generalized stress response that has escaped its usual counter-regulatory restraints (Gold, 1996). The stress system is active when the body is at rest, responding to many distinct circadian, neurosensory, blood-borne, and limbic signals. These signals include cytokines produced by immune-mediated inflammatory reactions, such as tumor necrosis factor a, interleukin-1 (IL-1), and interleukin-6 (IL-6) (Chrousos and Gold, 1992). On the other hand, locally, immune and immune accessory cells are activated, and cytokines, lipid mediators of inflammation and neuropeptides are generated (Paul and Seder, 1994). Usually these events are clinically silent, but inflammation occasionally causes an activation of the stress system and systemic symptoms and signs. Among the many mediators of inflammation, the three "inflammatory" cytokines TNFa, IL-la and p, and IL-6 are responsible for the strongest stimulation of the hypo-
* Dr. Anna Sluzewska died unexpectedly in early 1999. This is the last review she wrote.
Cytokines, Stress, and Depression, edited by Dantzer et at. Kluwer Academic / Plenum Publishers, New York, 1999.
thalamic-pituitary-adrenal (HPA) axis that is associated with immune/inflammatory reactions. Hypercortisolism is one of the most consistent findings in depression (Carroll et al., 1976; Nemeroff., 1996). There is substantial evidence from clinical studies that the hypercortisolemia seen in major depression is due to hypersecretion of corti-cotropin-releasing hormone (CRH) (Gold et al., 1994; Holsboer et al., 1984).
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