BACKGROUND: Infectious, autoimmune, and neurodegenerative diseases are associated with profound psychological disturbances. Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes. However, the mechanisms underlying the respective psychological alterations in humans have not been established yet. Therefore, we investigated the effects of low-dose endotoxemia, a well-established and safe model of host-defense activation, on emotional, cognitive, immunological, and endocrine parameters. METHODS: In a double-blind, crossover study, 20 healthy male volunteers completed psychological questionnaires and neuropsychological tests 1, 3, and 9 hours after intravenous injection ofSalmonella abortus equi endotoxin (0.8 ng/kg) or saline in 2 experimental sessions. Blood samples were collected hourly, and rectal temperature and heart rate were monitored continuously. RESULTS:Endotoxin had no effects on physical sickness symptoms, blood pressure, or heart rate. Endotoxin caused a mild increase in rectal temperature (0.5 degrees C), and increased the circulating levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors, interleukin (IL)-6, IL-1 receptor antagonist, and cortisol. After endotoxin administration, the subjects showed a transient significant increase in the levels of anxiety (effect size [ES] = 0.55) and depressed mood (ES = 0.66). Verbal and nonverbal memory functions were significantly decreased (ES = 0.55 to 0.64). Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety (r = 0.49 to r = 0.60), depressed mood (r = 0.40 to r = 0.75), and decreases in memory performance (r = 0.46 to r = 0.68). CONCLUSIONS: In humans, a mild stimulation of the primary host defense has negative effects on emotional and memory functions, which are probably caused by cytokine release. Hence, cytokines represent a novel target for neuropsychopharmacological research.
RCT Entities:
BACKGROUND: Infectious, autoimmune, and neurodegenerative diseases are associated with profound psychological disturbances. Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes. However, the mechanisms underlying the respective psychological alterations in humans have not been established yet. Therefore, we investigated the effects of low-dose endotoxemia, a well-established and safe model of host-defense activation, on emotional, cognitive, immunological, and endocrine parameters. METHODS: In a double-blind, crossover study, 20 healthy male volunteers completed psychological questionnaires and neuropsychological tests 1, 3, and 9 hours after intravenous injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in 2 experimental sessions. Blood samples were collected hourly, and rectal temperature and heart rate were monitored continuously. RESULTS: Endotoxin had no effects on physical sickness symptoms, blood pressure, or heart rate. Endotoxin caused a mild increase in rectal temperature (0.5 degrees C), and increased the circulating levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors, interleukin (IL)-6, IL-1 receptor antagonist, and cortisol. After endotoxin administration, the subjects showed a transient significant increase in the levels of anxiety (effect size [ES] = 0.55) and depressed mood (ES = 0.66). Verbal and nonverbal memory functions were significantly decreased (ES = 0.55 to 0.64). Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety (r = 0.49 to r = 0.60), depressed mood (r = 0.40 to r = 0.75), and decreases in memory performance (r = 0.46 to r = 0.68). CONCLUSIONS: In humans, a mild stimulation of the primary host defense has negative effects on emotional and memory functions, which are probably caused by cytokine release. Hence, cytokines represent a novel target for neuropsychopharmacological research.
Authors: Elisabeth G Vichaya; Phillip S Gross; Darlene J Estrada; Steve W Cole; Aaron J Grossberg; Scott E Evans; Michael J Tuvim; Burton F Dickey; Robert Dantzer Journal: Psychopharmacology (Berl) Date: 2019-02-26 Impact factor: 4.530
Authors: Christa M Helms; Ilhem Messaoudi; Sophia Jeng; Willard M Freeman; Kent E Vrana; Kathleen A Grant Journal: Alcohol Clin Exp Res Date: 2011-12-05 Impact factor: 3.455
Authors: Tristen K Inagaki; Keely A Muscatell; Michael R Irwin; Steve W Cole; Naomi I Eisenberger Journal: Neuroimage Date: 2011-11-04 Impact factor: 6.556
Authors: Shaoyong Su; Andrew H Miller; Harold Snieder; J Douglas Bremner; James Ritchie; Carisa Maisano; Linda Jones; Nancy V Murrah; Jack Goldberg; Viola Vaccarino Journal: Psychosom Med Date: 2008-12-10 Impact factor: 4.312
Authors: Joshua Hyong-Jin Cho; Michael R Irwin; Naomi I Eisenberger; Donald M Lamkin; Steve W Cole Journal: Neuropsychopharmacology Date: 2019-01-14 Impact factor: 7.853
Authors: Annemiek E Wolters; Arjen J C Slooter; Arendina W van der Kooi; Diederik van Dijk Journal: Intensive Care Med Date: 2013-01-18 Impact factor: 17.440