Haptoglobin Reduces Inflammatory Cytokine INF-γ and Facilitates Clot Formation in Acute Severe Burn Rat Model

  • Koami Hiroyuki
    Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University
  • Sakamoto Yuichiro
    Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University
  • Miyasho Taku
    Department of Veterinary Science, School of Veterinary Medicine, Rakuno Gakuen University
  • Noguchi Ryo
    Department of Thoracic and Cardiovascular Surgery, Faculty of Medicine, Saga University
  • Sato Norio
    Department of Primary Care & Emergency Medicine, Faculty of Medicine, Kyoto University
  • Kai Keita
    Department of Pathology, Saga University Hospital
  • Chris Yamada Kosuke
    Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University
  • Inoue Satoshi
    Division of Trauma Surgery and Surgical Critical Care, Faculty of Medicine, Saga University

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Abstract

<p>Haptoglobin exerts renal protective function by scavenging free hemoglobin from the urine and blood stream in patients with hemolytic disorders. Recent studies elucidate the relationships between haptoglobin and inflammation. In addition, coagulopathy is often induced by systemic inflammation characterized by the presence of vascular endothelial damage. We hypothesize that haptoglobin might have an anti-inflammatory effect and affect hypercoagulability using rat burn model. Thirty anesthetized rats of six-weeks of age received over 30% full-thickness scald burn on the dorsal skin surface. All rats were injected with either haptoglobin (Hpt) or normal saline (NS) intraperitoneally. The rats were divided into three groups: 1) control group (NS 20 mL/kg); 2) low concentration of Hpt group, L-Hpt, (Hpt 4 mL (80 U) /kg+NS 16 mL/kg); and 3) high concentration of Hpt group, H-Hpt, (Hpt 20 mL (400 U) /kg). While under anesthesia, all rats were euthanized by exsanguination at 6 hours (N=5) and 24 hours (N=5). Inflammatory and anti-inflammatory cytokines were measured and whole-blood viscoelastic tests were performed by thromboelastometry (ROTEM). Haptoglobin significantly reduced free hemoglobin 24 hours after the injury. Improvement of hematuria was confirmed in the H-Hpt group. There were no differences in thrombin-antithrombin complex and plasmin-α2 plasmin inhibitor complex. The haptoglobin tended to decrease interferon-gamma (IFN-γ) in H-Hpt group. ROTEM findings of the L-Hpt group showed significantly higher clot firmness and shorter time to maximum clot formation velocity than the control group. Haptoglobin reduced INF-γ, and accelerated speed of clot formation in acute phase of severe burn.</p>

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