The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection

Depression represents a major public health problem. It is estimated that 1 3-20% of the population has some depressive symptoms at any given time and about 5% of the population is assumed to suffer from major depression. Know n pathological processes include ischemia, neoplasia, necrosis, apoptosis, infection, and inflammation. Of those, inflammation is the most compatible with the waxing and waning course of depression, and could explain the biol ogy of this disorder that has a fluctuating course with severe episodes tha t can be followed by partial or complete remission. Over the years a body o f evidence has been accumulated suggesting that major depression is associa ted with dysfunction of inflammatory mediators. Major depression commonly c o-occurs with ischemic heart disease and decreased bone mineral density. De pressive symptoms are known to have a negative impact on cardiovascular pro gnosis, increasing the mortality rate of coronary artery disease. Several l ines of evidence indicate that brain cytokines, principally interleukin-1 b eta (IL-I beta) and IL-l receptor antagonist may have a role in the biology of major depression, and that they might additionally be involved in the p athophysiology and somatic consequences of depression as well as in the eff ects of antidepressant treatment. A particularly unique and novel aspect of the studies and views discussed here is their potential to lead to interve ntions which may reduce the morbidity and mortality risks for osteoporosis, cardiovascular disease, and behavioral symptoms in patients with major dep ression. We also discuss the emerging concept of peripheral and central cyt okine compartments: their integration and differential regulation is a key element for the optimal functioning of the immune and nervous systems.