Excessive Pro-Inflammatory Serum Cytokine Concentrations in Virulent Canine Babesiosis

Abstract

Babesia rossi infection causes a severe inflammatory response in the dog, which is the result of the balance between pro- and anti-inflammatory cytokine secretion. The aim of this study was to determine whether changes in cytokine concentrations were present in dogs with babesiosis and whether it was associated with disease outcome. Ninety-seven dogs naturally infected with B. rossi were studied and fifteen healthy dogs were included as controls. Diagnosis of babesiosis was confirmed by polymerase chain reaction and reverse line blot. Blood samples were collected from the jugular vein at admission, prior to any treatment. Cytokine concentrations were assessed using a canine-specific multiplex assay on an automated analyser. Serum concentrations of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-18, granulocyte-macrophage colony stimulating factor (GM-CSF) and monocyte chemotactic protein-1 (MCP-1) were measured. Twelve of the Babesia-infected dogs died (12%) and 85 survived (88%). Babesia-infected dogs were also divided into those that presented within 48 hours from displaying clinical signs, and those that presented more than 48 hours after displaying clinical signs. Cytokine concentrations were compared between the different groups using the Mann-Whitney U test. IL-10 and MCP-1 concentrations were significantly elevated for the Babesia-infected dogs compared to the healthy controls. In contrast, the IL-8 concentration was significantly decreased in the Babesia-infected dogs compared to the controls. Concentrations of IL-6 and MCP-1 were significantly increased in the non-survivors compared to the survivors. Concentrations for IL-2, IL-6, IL-18 and GM-CSF were significantly higher in those cases that presented during the more acute stage of the disease. These findings suggest that a mixed cytokine response is present in dogs with babesiosis caused by B. rossi, and that an excessive pro-inflammatory response may result in a poor outcome.

Canine Babesiosis: Where Do We Stand?

“…Also, the monocyte chemoattractant protein (MCP-1) and the keratinocyte chemotactic-like protein were the cytokines found in the study which could discriminate complicated from uncomplicated cases [105]. Those results are consistent with previously reported data for canine babesiosis caused by B. rossi in which non-survivors showed an increased concentration of MCP-1, indicating that this protein could be a marker of poor outcome [88]. A study of Zygner et al [106] showed an increase of tumor necrosis factor alpha (TNF-α) serum concentration during canine babesiosis caused by B. canis.…”

“…The possible causes are formation of platelet-leukocyte aggregates, sequestration, increased utilisation and reduced production [88,89]. One possible mechanism involved in leukopenia includes the ability of platelets to interact with leukocytes and induce their so-called ˝secondary capture˝.…”

Immunomodulatory in vitro effects of oclacitinib on canine T‐cell proliferation and cytokine production

“…The observed concentration of each analyte for each sample was calculated using a standard curve generated from the seven standards and a blank provided by the manufacturer. For each cytokine, multiplex data recorded out of range were assigned the respective lowest or highest extrapolated values; samples were not diluted and retested because of cost restraints . The values were reported in pg/mL.…”

Blood markers of fibrinolysis and endothelial activation in canine babesiosis

“…It has been reported that a proinflammatory state occurs in babesiosis that is associated with increased concentrations of markers of endothelial cell activation and altered hemostasis [6, 26]. Because canine babesiosis could be accompanied by endothelial dysfunction, the relationship between endothelial function and fibrinolytic balance needs to be examined in more detail.…”