Increased cytokine expression and concurrent psychiatric symptoms were initially observed after administration of cytokines to patients afflicted with cancer, hepatitis and multiple sclerosis. Cytokines are a diverse group of soluble messenger proteins involved in the regulation, repair of cells, and control of immune events. During an inflammatory event expression of CD4+ T-lymphocyte helper (Th)1 cells that primarily produce pro-inflammatory cytokines is favored which can lead to development of inflammatory disease (e.g., cardiovascular disease). Similarly, relationships have been shown to exist between changes in inflammatory mediator concentrations, specifically pro-inflammatory cytokines, and depression. An increased prevalence of depression in patients afflicted with co-morbid inflammatory disease indirectly supports this association. In further support, antidepressants have been suggested to alleviate symptoms of depression via anti-inflammatory actions. Administration of anti-cytokines to patients with concurrent depression and inflammatory disease has resulted in relief of depressive symptoms. The exact role of inflammation in development of depression, however, remains to be determined. Nevertheless, increased expression of inflammatory mediators in depressed patients occurs which may lead to variability in response to antidepressant drug therapy. For example, depressed patients non-responsive to drug treatment are reported to have increased cell mediated immunity shown by elevated CD4+ T-cell activity, pro-inflammatory cytokine expression, and stimulation of the acute phase response. This suggests a psycho-neuroimmunological approach may be required for optimal pharmacotherapy.