Cães com sepse apresentam aumento da concentração da proteina C reativa, mas não da HMGB1 / Increased concentrations of C-reactive protein but not high-mobility group box 1 in dogs with naturally occurring sepsis

Veterinary Immunology and Immunopathology

Available online 25 September 2013

In Press, Corrected Proof — Note to users

Research paper

Increased concentrations of C-reactive protein but not high-mobility group box 1 in dogs with naturally occurring sepsis

• I. Karlsson^a, , , 
• S. Wernersson^a, 
• A. Ambrosen^b, 
• H. Kindahl^b, 
• F. Södersten^c, 
• L. Wang^a, 
• R. Hagman^b

• ^a Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, Box 575, SE-75123 Uppsala, Sweden
• ^b Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, SE-75007 Uppsala, Sweden
• ^c Department of Pathology, Swedish University of Agricultural Sciences, Box 7028, SE-75007 Uppsala, Sweden

Abstract

Sepsis is difficult to diagnose and remains a common mortality cause worldwide in both humans and animals. The uterine infection pyometra causes sepsis in more than half of affected dogs and therefore allows the natural physiological development of sepsis to be studied. To find a sepsis-specific biochemical marker that could be combined with conventional clinical criteria for a more robust and quick diagnosis of sepsis, we measured systemic concentrations of high-mobility group box 1 (HMGB1) in 23 healthy control dogs and in 27 dogs with pyometra, 74% of which had sepsis. We also measured concentrations of the major acute phase protein C-reactive protein (CRP) and an indicator for endotoxaemia, prostaglandin F_2αmetabolite (PGM) to assess the relative contribution of HMGB1 to the detection of systemic inflammation and endotoxaemia. We found that HMGB1 concentrations, in line with concentrations of CRP and PGM, were significantly increased in dogs with pyometra, and that concentrations of CRP, but not HMGB1, were significantly higher in dogs with sepsis compared to dogs without sepsis. Although serum HMGB1 did not differ between dogs with or without sepsis and was not correlated with either CRP or PGM concentrations, HMGB1 was correlated with the total white blood cell counts, suggesting an independent regulation and involvement in inflammation.

Keywords

• Sepsis; 
• SIRS; 
• Biomarkers; 
• Diagnostics; 
• Cytokines; 
• Canine/dog; 
• Pyometra; 
• Bacterial uterine infection;
• Inflammation; 
• HMGB1; 
• CRP; 
• PGM

• Table 1. Clinical and laboratory variables in dogs with pyometra.^a

  Parametersb	P+SIRS+ (n = 20)	P+SIRS− (n = 7)	Controls (n = 23)
  Body temp (°C)	39.3 (38.9–39.7)	38.5 (38.2–38.9)	38.2 (38.1–38.3)
  HR (counts/min)	100 (86.5–127)	100 (85–100)	96 (84–102)
  RR (counts/min)	29 (24.5–82.5)	16 (16–18)	16 (16–21)
  WBC (cells ×109/L)	20.7 (18.2–25.6)	11.5 (10.4–14.2)	9.8 (8.2–12)
  PBN (%)	26.4 (10.8–74.7)	16.8 (2.9–36.7)	0.77 (0.0–4.76)
  Lymph (cells ×109/L)	1.8 (1.0–2.6)	1.45 (0.95–1.75)	2.4 (1.7–3.3)
  Mono (cells ×109/L)	2.35 (1.65–3.8)	0.4 (0.25–1.6)	0.4 (0.3–0.7)
  Eosin (cells ×109/L)	0.0 (0.0–0.65)	0.4 (0.05–0.6)	0.5 (0.2–1.4)
  Baso (cells ×109/L)	0.0 (0.0–0.0)	0.0 (0.0–0.0)	0.0 (0.0–0.1)
  ALAT (μkat/L)	0.3 (0.2–0.4)	0.4 (0.3–1.4)	0.5 (0.4–0.7)
  Bile acids (g/L)	1.85 (0.65–3.95)	2.5 (0.8–2.6)	3.8 (1.8–5.7)
  Crea (μmol/L)	62 (54.5–76)	53 (48–62)	76 (61–80)