Illness, Cytokines, and Depression

Abstract

A BSTRACT : Various medical conditions that involve activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression. In this review we present our recent studies, designed to investigate the relationship between the behavioral effects of immune activation and depressive symptomatology. In the first set of experiments, we used a double-blind prospective design to investigate the psychological consequences of illness in two models: (1) vaccination of teenage girls with live attenuated rubella virus, and (2) lipopolysaccharide (LPS) administration in healthy male volunteers. In the rubella study, we demonstrated that, compared to control group subjects and to their own baseline, a subgroup of vulnerable individuals (girls from low socioeconomic status) showed a significant virus-induced increase in depressed mood up to 10 weeks after vaccination. In an ongoing study on the effects of LPS, we demonstrated significant LPSinduced elevation in the levels of depression and anxiety as well as memory deficits. These psychological effects were highly correlated with the levels of LPS-induced cytokine secretion. In parallel experiments, we demonstrated in rodents that immune activation with various acute and chronic immune challenges induces a depressive-like syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. Chronic treatment with antidepressants (imipramine or fluoxetine) attenuated many of the behavioral effects of LPS, as well as LPS-induced changes in body temperature, adrenocortical activation, hypothalamic serotonin release, and the expression of splenic TNF-␣ mRNA. Taken together, these findings suggest that cytokines are involved in the etiology and symptomatology of illness-associated depression.

Intrahippocampal Transplantation of Transgenic Neural Precursor Cells Overexpressing Interleukin-1 Receptor Antagonist Blocks Chronic Isolation-Induced Impairment in Memory and Neurogenesis

“…IL-1 receptors are localized in several areas of the rodent brain, with the highest densities detected in the hippocampus (Loddick et al, 1998). Brain IL-1 is induced by many immune challenges, as well as by exposure to psychological stressors, and can produce marked neural, neuroendocrine, and behavioral alterations (Besedovsky and del-Rey, 1996;Rothwell and Luheshi, 2000;Yirmiya et al, 2000).…”

The Role of Immune System in Depression Disorder

“…However, chronic exposure to inflammatory cytokines with high concentration may lead to neuropsychiatric dysfunction with depression being a common one. Compared to the general population, patients with medical illnesses with elevated level of inflammatory cytokines were more prone to depression [46] [47].…”

The Proinflammatory Cytokines Interleukin-1beta and Tumor Necrosis Factor-Alpha Activate Serotonin Transporters

“…Conversely, therapeutic treatments with proinflammatory cytokines result in 'sickness behavior' that is similar in many respects to depression, with decreased appetite, anorexia, weight loss, fatigue, loss of libido, sleep disturbances, and reduced social contact (Kent et al, 1996;Yirmiya et al, 2000;Dantzer, 2001), and depression is frequently observed in association with peripheral inflammatory cytokine activation in a number of medical conditions including viral infections, rheumatoid arthritis, cancer, and neurodegenerative diseases (Meijer et al, 1988;Hall and Smith, 1996;Yirmiya et al, 1999;Pollak et al, 2000). Additionally, in human volunteers, depression, anxiety, and memory impairment are associated with immune activation by the bacterial endotoxin, lipopolysaccharide, and are correlated with serum IL-1b and TNF-a levels induced by that treatment (Yirmiya et al, 2000).…”