The article discusses the relationship between inflammation and depression, highlighting how the immune system can influence brain function and behavior. When the body is infected, innate immune cells produce pro-inflammatory cytokines that affect the brain, leading to sickness behavior, characterized by changes in mood, appetite, sleep, and cognitive function. If this immune response continues, it can exacerbate sickness and even trigger symptoms of depression in vulnerable individuals. The brain, despite being considered an "immune-privileged" organ, can still be influenced by peripheral immune signals through various pathways, including afferent nerves, humoral pathways, and cytokine transporters at the blood-brain barrier. Pro-inflammatory cytokines like IL-1β and TNF-α are key players in these processes, causing a range of behavioral effects. The article also explores the role of tryptophan metabolism and the kynurenine pathway in depression, suggesting that altered tryptophan levels and the production of neuroactive metabolites may contribute to depressive symptoms. Additionally, it discusses alternative mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis and glucocorticoid receptor resistance, which can further enhance the depressive response. The neuroanatomical basis of cytokine-induced depression is also examined, focusing on brain regions involved in emotion processing and psychomotor retardation. Finally, the article highlights the implications for depression in medically ill patients, suggesting that inflammation may play a significant role in the development of depression in these individuals.The article discusses the relationship between inflammation and depression, highlighting how the immune system can influence brain function and behavior. When the body is infected, innate immune cells produce pro-inflammatory cytokines that affect the brain, leading to sickness behavior, characterized by changes in mood, appetite, sleep, and cognitive function. If this immune response continues, it can exacerbate sickness and even trigger symptoms of depression in vulnerable individuals. The brain, despite being considered an "immune-privileged" organ, can still be influenced by peripheral immune signals through various pathways, including afferent nerves, humoral pathways, and cytokine transporters at the blood-brain barrier. Pro-inflammatory cytokines like IL-1β and TNF-α are key players in these processes, causing a range of behavioral effects. The article also explores the role of tryptophan metabolism and the kynurenine pathway in depression, suggesting that altered tryptophan levels and the production of neuroactive metabolites may contribute to depressive symptoms. Additionally, it discusses alternative mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis and glucocorticoid receptor resistance, which can further enhance the depressive response. The neuroanatomical basis of cytokine-induced depression is also examined, focusing on brain regions involved in emotion processing and psychomotor retardation. Finally, the article highlights the implications for depression in medically ill patients, suggesting that inflammation may play a significant role in the development of depression in these individuals.