Document Detail


Gender differences in the innate immune response and vascular reactivity following the administration of endotoxin to human volunteers.
MedLine Citation:
PMID:  17452928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine gender differences in the innate immune response and vascular reactivity during human endotoxemia. DESIGN: Clinical experimental study. SETTING: University medical center intensive care research unit. SUBJECTS: Fifteen female and 15 male volunteers. INTERVENTIONS: Intravenous injection of 2 ng/kg Escherichia coli lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: C-reactive protein, leukocytes, and cytokines were measured at regular time intervals as indicators of inflammation. Heart rate and blood pressure were continuously monitored. Forearm blood flow and the responsiveness of forearm vessels to the intrabrachial infusion of norepinephrine (1-3-10-30 ng/min/dL) were measured before and 4 hrs after the administration of endotoxin using venous occlusion plethysmography. Differences were tested with repeated-measures analysis of variance. Females showed a more proinflammatory response to lipopolysaccharide than males, illustrated by a higher rise in C-reactive protein (42 +/- 3 vs. 29 +/- 3 mg/L, p = .002) and more leukocyte sequestration (leukopenia 1.8 +/- 0.1 x 10 vs. 2.4 +/- 0.1 x 10, p = .003). The increase in cytokine levels showed a more proinflammatory pattern in females as reflected by a higher increase in tumor necrosis factor-alpha (965 +/- 193 vs. 411 +/- 35 pg/mL, p < .0001), whereas the increase of the anti-inflammatory interleukin-10 was not significantly different (95 +/- 15 pg/mL in females vs. 129 +/- 15 pg/mL in males, p = .288). Females exhibited higher baseline levels (9.9 +/- 1.1 vs. 7.0 +/- 0.8 pg/mL in males, p = .042) and an augmented increase in lipopolysaccharide-binding protein, which may explain the more pronounced inflammatory response in females. The lipopolysaccharide-induced change in heart rate was not significantly different between the genders, whereas blood pressure decreased more in females (p < .0001). Lipopolysaccharide administration significantly attenuated the norepinephrine sensitivity in males (p = .002), whereas no lipopolysaccharide-induced effect was observed in females (p = .552; difference between groups, p = .045). CONCLUSIONS: During experimental human endotoxemia, females showed a more pronounced proinflammatory innate immune response associated with less attenuation of norepinephrine sensitivity. These findings may be relevant in view of the profound and incompletely explained differences in incidence and outcome of sepsis among male and female patients.
Authors:
Lucas T van Eijk; Mirrin J Dorresteijn; Paul Smits; Johannes G van der Hoeven; Mihai G Netea; Peter Pickkers
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  35     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-24     Completed Date:  2007-07-02     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1464-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Circulation*
Blood Pressure
C-Reactive Protein / immunology
Cytokines / immunology
Dose-Response Relationship, Drug
Endotoxemia / immunology*,  physiopathology
Escherichia coli*
Female
Fever / immunology
Forearm / blood supply
Heart Rate
Humans
Immunity, Innate*
Intensive Care Units
Leukocytes / immunology
Lipopolysaccharides / blood,  immunology*
Male
Regional Blood Flow
Sex Factors
Chemical
Reg. No./Substance:
0/Cytokines; 0/Lipopolysaccharides; 9007-41-4/C-Reactive Protein
Comments/Corrections
Comment In:
Crit Care Med. 2007 Jun;35(6):1610-2   [PMID:  17522533 ]

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