Journal
INFLAMMATION RESEARCH
Volume 59, Issue 7, Pages 511-518Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00011-009-0155-y
Keywords
Inflammation; Cytokine; Nitric oxide; Anticoagulant; Heat stress
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Systemic inflammatory mediators, including the high mobility group box 1 (HMGB1) protein, play important roles in the development of various inflammatory conditions. Although anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, their anti-inflammatory mechanism of action is not well understood. Nevertheless, as heat stroke is a severe inflammatory response disease, we hypothesized that AT III would inhibit inflammation and prevent heat stress-induced acute heat stroke. Male Wistar rats received a bolus injection of saline or 250 U of AT III per kg of body weight into the tail vein, followed by heat stress (exposure to 42A degrees C for 30 min). Levels of cytokines (interleukin-1 beta, interleukin-6, and TNF-alpha), NOx, and HMGB1 were measured in serum and tissue at regular intervals for 6 h after the heat stress induction. Levels of cytokines, NOx, and HMGB1 in serum decreased over time in AT III-treated rats. AT III pretreatment also reduced NOx levels during heat stress-induced inflammation. As a result, AT III pretreatment improved survival in a rat model of heat stress-induced acute inflammation. Our data suggest that AT III pretreatment inhibited the secretion of cytokines, NOx, and HMGB1, and prevented heat stress-induced acute inflammation.
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