Recombinant thrombomodulin prevents heatstroke by inhibition of high-mobility group box 1 protein in sera of rats.
Heatstroke, a severe inflammatory response disease, is a medical emergency characterized by high body temperature. The protein C anticoagulant system inhibits inflammation resulting from various causes. Thrombomodulin (TM), a widely expressed glycoprotein originally identified in vascular endothelium, is an important cofactor in the protein C anticoagulant system. We tested the hypothesis that TM could prevent acute inflammation induced by heat stress in a rodent model. Male Wistar rats received a bolus of 1 mg x kg of body weight of TM or saline injected into the tail vein, followed by heat-stress treatment (exposure to 42°C for 30 min). Serum concentrations of cytokines (IL-1β, IL-6, and TNF-α), NO, and high-mobility group box 1 (HMGB1) protein were measured at various time points after treatment. We observed a decrease in the levels of cytokines and HMGB1 protein in sera of TM-treated animals over time. Inhibition of NO overproduction by recombinant TM was observed during heat stress-induced inflammation. Because of the decline in inflammatory marker levels, TM ameliorated injury to various organs in the rat model of heat stress-induced acute inflammation. As TM exhibited a strong anti-inflammatory effect in a rat model of acute inflammation induced by heat stress, TM represents a potential therapeutic for heatstroke prevention or management in patients.
Hagiwara
Satoshi
S
Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan. saku@med.oita-u.ac.jp
Iwasaka
Hideo
H
Goto
Koji
K
Ochi
Yoshifumi
Y
Mizunaga
Shouichi
S
Saikawa
Tetsunori
T
Noguchi
Takayuki
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood* / Q000378:metabolism; D018883:Heat Stroke / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018180:Thrombomodulin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D024243:HMGB1 Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha