[HTML][HTML] Hemopexin in severe inflammation and infection: mouse models and human diseases
T Lin, D Maita, SR Thundivalappil, FE Riley… - Critical care, 2015 - Springer
T Lin, D Maita, SR Thundivalappil, FE Riley, J Hambsch, LJ Van Marter, HA Christou…
Critical care, 2015•SpringerIntroduction Cell-free plasma hemoglobin is associated with poor outcome in patients with
sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the
presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma
protein that binds heme with extraordinary affinity, blocks these effects and has been
proposed as a possible treatment approach to decrease inflammation in critically ill patients.
Methods We studied mouse models of endotoxemia, burn wound infections and peritonitis in …
sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the
presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma
protein that binds heme with extraordinary affinity, blocks these effects and has been
proposed as a possible treatment approach to decrease inflammation in critically ill patients.
Methods We studied mouse models of endotoxemia, burn wound infections and peritonitis in …
Introduction
Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed as a possible treatment approach to decrease inflammation in critically ill patients.
Methods
We studied mouse models of endotoxemia, burn wound infections and peritonitis in order to assess if a repletion strategy for hemopexin might be reasonable. We also measured hemopexin in small numbers of three patient populations that might be logical groups for hemopexin therapy: patients with sepsis and ARDS, patients with severe burns, and premature infants.
Results
Despite severe disease, mean plasma hemopexin levels were increased above baseline in each murine model. However, plasma hemopexin levels were decreased or markedly decreased in many patients in each of the three patient populations.
Conclusions
Potentially different behavior of hemopexin in mice and humans may be important to consider when utilizing murine models to represent acute human inflammatory diseases in which heme plays a role. The findings raise the possibility that decreased hemopexin could result in insufficiently neutralized or cleared heme in some patients with ARDS, burns, or in premature infants who might be candidates to benefit from hemopexin administration.
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