Both psychological stress (e.g., academic stress, depression) and physical stress (e.g., infection, trauma) can activate central cytokine expression. Activation of central pro-inflammatory cytokines is associated with various phenomena, both peripherally (e.g. cascade activation of other cytokines, induction of acute phase proteins) and centrally (e.g., various immunologic, neurochemical, neuroendocrine and behavioral effects). Autonomic nervous system innervation of lympoid tissue is shown. Feedback mechanisms occur at several levels and include negative feedback exerted by cortisol. IL= interleukin, TNFa- tumor necrosis factor a, IFN- interferon, CRH- corticotropin-rleasing hormone, GnRh=gonadotropin releasing hormone, NE= norepinephrine,, 5HT=serotonin, DA=dopamine, NK=natural killer. (Adapted from Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease. Arch Gen Psychiatry 1998; 55:580-592 and Kronfol, Z., & Remick, D.G.. Cytokines and the brain: implications for clinical psychiatry. American Journal of Psychiatry 2000; 683-694.)