Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans
Publication Date
December 02, 2011
Journal
PLOS ONE
Authors
Jan Sebastian Grigoleit, Jennifer S. Kullmann, Oliver T. Wolf, Florian Hammes, et al
Volume
6
Issue
12
Pages
e28330
DOI
https://dx.plos.org/10.1371/journal.pone.0028330
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0028330
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22164271
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229570
Europe PMC
http://europepmc.org/abstract/MED/22164271
Web of Science
000298171400072
Scopus
82555170607
Mendeley
http://www.mendeley.com/research/dosedependent-effects-endotoxin-neurobehavioral-functions-humans
Events
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Mendeley | Further Information

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CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/358532", "https://ndownloader.figshare.com/files/358579"], "description"=>"<div><p>Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.4 (<em>n</em> = 18) or 0.8 ng/kg of body weight (<em>n</em> = 16). Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task) and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System). Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1ra), salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the <em>high-dose</em> LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.</p> </div>", "links"=>[], "tags"=>["dose-dependent", "effects", "endotoxin", "neurobehavioral", "functions", "humans"], "article_id"=>130879, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0028330.s001", "https://dx.doi.org/10.1371/journal.pone.0028330.s002"], "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dose_Dependent_Effects_of_Endotoxin_on_Neurobehavioral_Functions_in_Humans/130879", "title"=>"Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-12-02 00:14:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/707771"], "description"=>"<p>Absolute changes in mood, calmness, and alertness (MDBF) and in state anxiety (STAI) after administration of 0.4 (solid lines, <i>n</i> = 18) or 0.8 ng/kg <i>E. coli</i> endotoxin (dashed lines, <i>n</i> = 16). Data are presented as means ± SEM. Significant differences between experimental condition and respective saline control: *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001; significant differences between changes in <i>high-</i> and <i>low-dose</i> condition: ##<i>p</i><0.01, ###<i>p</i><0.001 (Bonferroni post hoc test).</p>", "links"=>[], "tags"=>["immunology", "Mental health", "physiology", "neuroscience"], "article_id"=>378120, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028330.g005", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LPS_effects_on_mood_and_anxiety_/378120", "title"=>"LPS effects on mood and anxiety.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-02 02:15:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/707388"], "description"=>"<p>Absolute changes in body temperature and heart rate following the administration of 0.4 (solid lines, <i>n</i> = 18) or 0.8 ng/kg <i>E. coli</i> endotoxin (dashed lines, <i>n</i> = 16). Data are presented as means ± SEM. Significant differences between experimental condition and respective saline control: *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 (Bonferroni post hoc test).</p>", "links"=>[], "tags"=>["immunology", "Mental health", "physiology", "neuroscience"], "article_id"=>377737, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028330.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Body_temperature_and_heart_rate_/377737", "title"=>"Body temperature and heart rate.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-02 02:08:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/708124"], "description"=>"<p>Long-term memory performance for emotionally arousing and neutral stimuli after administration of LPS (black bars) or saline (white bars). Left panel: <i>low-dose</i> group with subjects who received 0.4 ng LPS per kg of body weight. Right panel: <i>high-dose</i> group with subjects who received 0.8 ng/kg. Data are presented as means ± SEM. Significant differences between the two groups or between experimental condition and respective saline control: *<i>p</i><0.05 (Bonferroni corrected t-test). Except for the <i>low-dose</i> LPS condition, memory performance was always significantly higher for emotional than for neutral stimuli (Bonferroni corrected t-tests, not illustrated).</p>", "links"=>[], "tags"=>["immunology", "Mental health", "physiology", "neuroscience"], "article_id"=>378475, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028330.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Long_term_memory_performance_/378475", "title"=>"Long-term memory performance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-02 02:21:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/707484"], "description"=>"<p>Absolute changes in plasma concentrations of pro- (IL-6, TNF-α) and anti-inflammatory (IL-10, IL-1ra) cytokines after administration of 0.4 (solid lines, <i>n</i> = 18) or 0.8 ng/kg <i>E. coli</i> endotoxin (dashed lines, <i>n</i> = 16). Data are presented as means ± SEM. Significant differences between experimental condition and respective saline control: *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001; significant differences between changes in <i>high</i>- and <i>low-dose</i> condition: ##<i>p</i><0.01, ###<i>p</i><0.001 (Bonferroni post hoc test).</p>", "links"=>[], "tags"=>["lps"], "article_id"=>377836, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028330.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_response_to_LPS_administration_/377836", "title"=>"Cytokine response to LPS administration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-02 02:10:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/707626"], "description"=>"<p>Absolute changes in plasma concentrations of cortisol and norepinephrine and salivary cortisol levels after administration of 0.4 (solid lines, <i>n</i> = 18) or 0.8 ng/kg <i>E. coli</i> endotoxin (dashed lines, <i>n</i> = 16). Data are presented as means ± SEM. Significant differences between experimental condition and respective saline control: *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001 (Bonferroni post hoc test).</p>", "links"=>[], "tags"=>["responses", "lps"], "article_id"=>377978, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028330.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neuroendocrine_responses_to_LPS_administration_/377978", "title"=>"Neuroendocrine responses to LPS administration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-02 02:12:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/707951"], "description"=>"<p>Accuracy (A) and reaction time (B) in the computerized n-back working memory task (2-back version) 2 h after administration of endotoxin (black bars) or saline (white bars) within the same individuals, respectively. The <i>low-dose</i> group receiving 0.4 ng <i>E. coli</i> endotoxin per kg of body weight is represented on the left, and the <i>high-dose</i> group receiving 0.8 ng/kg on the right. The maximum possible accuracy score in (A) was 25. Data are presented as means ± SEM. Significant differences between experimental condition and respective saline control: **<i>p</i><0.01 (Bonferroni post hoc test).</p>", "links"=>[], "tags"=>["immunology", "Mental health", "physiology", "neuroscience"], "article_id"=>378299, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028330.g006", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Working_memory_performance_/378299", "title"=>"Working memory performance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-02 02:18:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/707314"], "description"=>"<p>Volunteers arrived 1 h prior to the experiment. Thirty minutes before the injection, an intravenous cannula was inserted into the antecubital forearm vein for intermittent blood sampling and drug injection. Before and 1, 1.75, 3, 4, and 6 h after the injection blood samples (B) were collected and vital parameters were assessed. Before as well as 3 and 6 h after the injection the subjects completed mood and anxiety questionnaires (M). After the 1.75 h blood collection the n-back task was performed, and before the 3 h collection the acquisition for the long-term memory test took place. When showing no signs of inflammation or any other kind of illness, subjects were discharged and returned on the following day for follow-up examination and completing the long-term memory task. The whole procedure was repeated on another study day with a 10–14 days delay. Every participant received the higher or lower dose of LPS during one and saline during the other test session in a balanced, randomized manner.</p>", "links"=>[], "tags"=>["immunology", "Mental health", "physiology", "neuroscience"], "article_id"=>377663, "categories"=>["Physiology", "Neuroscience", "Mental Health", "Immunology"], "users"=>["Jan-Sebastian Grigoleit", "Jennifer S. Kullmann", "Oliver T. Wolf", "Florian Hammes", "Alexander Wegner", "Stephanie Jablonowski", "Harald Engler", "Elke Gizewski", "Reiner Oberbeck", "Manfred Schedlowski"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0028330.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experimental_design_/377663", "title"=>"Experimental design.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-12-02 02:07:43"}

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