Many interactions occur between the immune, neural, and psychological systems. These interactions include communication pathways from the brain to the immune system, particularly the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system, that mediate the influence of psychological variables, such as stress and emotions, on immunity and resistance to disease.1
In addition, when the body is confronted by pathogens, the immune system serves as a sensory organ, alerting the brain to the presence of infection-induced immune activation.2 The communication from the immune system to the brain is mediated by cytokines, which are peptides that orchestrate the immune response with a wide range of other biologic activities. During immune stimulation, cytokines such as interleukins and interferons are produced both in the periphery and in the brain, where they can affect neural, neuroendocrine, and behavioral functions through specific receptors.2,3
In addition to physiologic responses, such as fever, and hormonal responses, such as activation of the HPA axis, brain cytokines also produce behavioral changes. A person with a physical illness may show depressed mood, anorexia, weight loss, sleepiness and altered sleep patterns, fatigue and retardation of motor activity, reduced interest in the physical and social environment, and impaired cognitive abilities.3,4 During an acute infection, these behavioral symptoms, collectively termed “sickness behavior,” are considered to be an adaptive response, rather than due to the disease process itself and the fever that accompanies it. However, during chronic infections and other chronic medical conditions associated with intense immune activation, the sickness behavior syndrome can develop into a depressive episode. Illness-associated depression can cause high levels of distress in a sick person and may further complicate the existing physical symptoms and compliance with therapy.
In this review, I present the current knowledge on the role of cytokines in mediating the depressive symptoms that accompany various medical conditions. I also consider the possible use of antidepressant drugs—and their mechanism of action—in the treatment of illness-associated depression.