High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis.
OBJECTIVE
Intravenous immunoglobulin therapy has been proposed as an advanced treatment for sepsis. Yet, its benefit remains unclear and the mechanism of action is poorly understood. One key mediator in the development of sepsis is high mobility group box 1 (HMGB1). Therefore, we examined the serum and lung tissue levels of HMGB1 in a rat model of sepsis.


METHODS
Prospective controlled animal study in a university laboratory.


METHODS
Rats received either cecal ligation and puncture-induced sepsis or had additional intravenous immunoglobulin treatment in boluses of 100, 300, or 1,000 mg/kg.


RESULTS
After induction of sepsis and respective treatment conditions, histopathology, wet/dry weight ratios, and signaling molecules were examined in pulmonary tissue. Serum and pulmonary levels of cytokine and HMGB1 were measured. High dose intravenous immunoglobulin (1,000 mg/kg)-treated animals demonstrated significantly improved survival and pulmonary histopathology compared to the control rats. Serum and pulmonary HMGB1 levels were lower over time among intravenous immunoglobulin-treated animals. Furthermore, administration of intravenous immunoglobulin resulted in inhibition of NF-kappaB activity.


CONCLUSIONS
High-dose intravenous immunoglobulin decreased the mortality and pulmonary pathology in a rat model of sepsis. A significant reduction in HMGB1 levels was also observed, which may be mediated by inhibition of inflammation and NF-kappaB.


BACKGROUND
23. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI): experimental models.
Hagiwara
Satoshi
S
Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan. saku@med.oita-u.ac.jp
Iwasaka
Hideo
H
Hasegawa
Akira
A
Asai
Nobuhiko
N
Noguchi
Takayuki
T
D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood / Q000378:metabolism*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000517:prevention & control; D018805:Sepsis / Q000150:complications / Q000628:therapy*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D024243:HMGB1 Protein; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha