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

Hiroyuki Koami¹, Yuichiro Sakamoto¹, Taku Miyasho², Ryo Noguchi³, Norio Sato⁴, Keita Kai⁵, Kosuke Chris Yamada¹ and Satoshi Inoue⁶

¹Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, Saga, Japan
²Department of Veterinary Science, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan
³Department of Thoracic and Cardiovascular Surgery, Faculty of Medicine, Saga University, Saga, Japan
⁴Department of Primary Care & Emergency Medicine, Faculty of Medicine, Kyoto University, Kyoto, Japan
⁵Department of Pathology, Saga University Hospital, Saga, Japan
⁶Division of Trauma Surgery and Surgical Critical Care, Faculty of Medicine, Saga University, Saga, Japan

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.

J Nippon Med Sch 2017; 84: 64-72

Keywords
haptoglobin, severe burn, IFN-γ, clot formation, thromboelastometry

Correspondence to
Hiroyuki Koami, MD, Department of Emergency and Critical Care Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga city, Saga 849-8501, Japan
hkoami@cc.saga-u.ac.jp

Received, March 23, 2016
Accepted, December 20, 2016