Protease inhibitors, inflammatory markers, and their association with outcome in dogs with naturally occurring acute pancreatitis

Abstract

Background: Acute pancreatitis (AP) presumably is associated with pancreatic protease activation, protease inhibitor (PI) depletion, and inflammatory mediator secretion.

Objectives: Examine PIs and inflammatory mediator concentrations in dogs with AP and their association with death.

Animals: Thirty-one dogs diagnosed with AP based on clinical signs, ultrasonographic findings, and increased canine pancreatic lipase immunoreactivity (cPLI) and 51 healthy control dogs.

Methods: Antithrombin and α₂ -antiplasmin activity (ATA and α₂ AP, respectively) and concentrations of α₁ -proteinase inhibitor (α₁ PI), α₂ -macroglobulin (α₂ MG), C-reactive protein (CRP), interleukins (ILs)-2,6,8 and tumor necrosis factor-α (TNF-α) were prospectively measured. Severity of AP was assessed by clinical severity scoring systems.

Results: Mortality rate was 19%. Antithrombin activity was lower (P = .004) and maximal CRP, IL-6, and TNF-α concentrations higher (P < .04) in the AP group compared to the controls, whereas IL-2, IL-8, α₁ PI, and α₂ AP concentrations did not differ between groups. Serum α₂ MG concentration was not reliably detected. Serum cPLI, CRP, and IL-6 concentrations were significantly and positively correlated. The ATA was lower (P = .04), and canine acute pancreatitis severity (CAPS) scores higher (P = .009) in nonsurvivors compared to survivors. Higher CAPS scores were associated (P < .05) with decreased ATA and increased cPLI, CRP, and IL-6 concentrations.

Conclusions and clinical importance: Systemic inflammation in dogs with AP is manifested by increased inflammatory mediator concentrations, correlating with cPLI and CRP concentrations. Hypoantithrombinemia is associated with death. Serum concentrations of α₂ AP and α₁ PI are less useful prognostic markers. The CAPS score is a useful prognostic marker in dogs with AP.

Keywords: C-reactive protein; antithrombin; canine; cytokine; interleukin; α1-proteinase inhibitor; α2-antiplasmin.