
Hypothermia enhances the biological activity of lipopolysaccharide by altering its fluidity state
Author(s) -
Luhm Jürgen,
Schromm Andra Beate,
Seydel Ulrich,
Brandenburg Klaus,
Wellinghausen Nele,
Riedel Eberhard,
Schumann Ralf Reiner,
Rink Lothar
Publication year - 1998
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1998.2560325.x
Subject(s) - lipopolysaccharide , lipid a , chemistry , superantigen , tumor necrosis factor alpha , membrane fluidity , cytokine , sepsis , escherichia coli , hypothermia , interleukin 6 , heat shock , chemotype , microbiology and biotechnology , heat shock protein , bacteria , biochemistry , biology , immunology , staphylococcus aureus , medicine , food science , genetics , membrane , gene , essential oil
Lipopolysaccharides (LPS, endotoxin) of Gram‐negative bacteria are among the main causes of sepsis and septic shock. In the present study, the influence of temperature on the biological activity of LPS was investigated. Lowering the temperature from 37 +C to 34.5 +C or to 30 +C significantly enhances in vitro tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β and IL‐6 release induced by different LPS chemotypes and heat‐inactivated Escherichia coli . This cytokine‐increasing effect of lowering the temperature is highly mediated by serum proteins, particularly by LPS‐binding protein (LBP) and low‐density lipoproteins (LDL). In contrast, cytokine production induced by the superantigen toxic shock syndrome toxin‐1 (TSST‐1) from Gram‐positive Staphyloccoccus aureus decreases by around 70 % at 30 +C as compared with 37 +C, corresponding to the expected effect of change in temperature and regardless of the presence of serum proteins. In order to explain the unexpected biological hypothermia effect with regard to LPS, the fluidity state of the lipid A portion of LPS as one important physico‐chemical property possibly involved was investigated. The fluidity, determined by fluorescence polarization measurements, was found to decrease with decreasing temperature. These data suggest that a low fluid LPS chemotype is biologically more active than a more fluid one (and vice versa ). Statistical analysis of the results shows a strong correlation between cytokine secretion and fluidity state of a given LPS chemotype (0.71 < r < 0.89, all P < 0.01). As a clinical consequence, these data may be one possible explanation for the higher mortality rate of hypothermic Gram‐negative sepsis.