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

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 2α metabolite (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.

Serum alpha1‐proteinase inhibitor concentrations in dogs with systemic inflammatory response syndrome or sepsis

“…Serum CRP quantification was included in this study as this major positive APP has been well studied in canine inflammatory conditions and/or infections, and the results of our study largely agree with those of others. However, it is currently unknown whether genetic polymorphisms in the CRP gene or its promoter genes exist in dogs, similar to those in people, and their potential contribution to the high interindividual variation seen in dogs …”

“…Proinflammatory cytokines such as interleukin‐6 (IL‐6), which induces mainly type II APPs, and tumor necrosis factor‐alpha (TNF‐α), which induces type I APPs, have been demonstrated to be upregulated in dogs with sepsis or noninfectious systemic inflammatory response syndrome (SIRS) but not to distinguish between them . C‐reactive protein (CRP), a type I APP of the pentraxin family, has been shown to have prognostic utility in dogs with sepsis or SIRS but also lacks the ability to discriminate sepsis from noninfectious SIRS …”

Evaluation of the host cytokine response in dogs with sepsis and noninfectious systemic inflammatory response syndrome

“…Several studies have measured blood HMGB‐1 concentrations in dogs . In dogs with GDV, high HMGB‐1 concentrations were associated with gastric necrosis and with nonsurvival .…”

Plasma iron, C‐reactive protein, albumin, and plasma fibrinogen concentrations in dogs with systemic inflammatory response syndrome

“…CRP has been identified during inflammation in several species including dogs, 25 and increased levels of this APP have been linked to the presence of various disorders, 26 and also their extent and severity. 5,[27][28][29][30][31][32] CRP in dogs is considered a major APP (10-to 100-fold increase in response to inflammatory stimuli) and has a short half-life (24-48 h). 4,11,33 In our study, dogs with SIRS/sepsis showed higher mean CRP concentrations than dogs with local inflammation.…”