Table 1.
Possible roles of pro-inflammatory cytokines in the development of anemia in canine babesiosis.
| Cytokines | Action | Reference |
|---|---|---|
| TNF-α | Induction of CXCL8 and CXCL1 gene expression. Together with IFN-γ, induction of monocyte to macrophage differentiation. Stimulation of nitric oxide synthesis. Increased expression of CSF-2. Contribution to secretion of properdin leading to alternative pathway of complement activation. Increased expression of ICAM-1 and VCAM-1. | [73,74,75,76,81,140,238,264,265,270] |
| IFN-γ | Contribution to classical activation of macrophages leading to release of IL-6 and TNF-α. Contribution to splenic response to infection (induction of progenitor cells in bone marrow which differentiate to monocytes migrating to the spleen). Increased expression of ICAM-1. | [140,145,255,264,265] |
| IL-6 | Influence on development of oxidative stress. Stimulation of IgG1 production. Activation of Th1 lymphocytes. Stimulation of IgM production (inhibited by IFN-γ). Contribution to activation of complement system. Increased expression of ICAM-1. | [140,152,153,154,188,189,192,195,232,264,265] |
| IL-12 | Together with IL-18, triggering IFN-γ and TNF-α action. In synergy with IL-18, inducing production of mitochondrial reactive oxygen species. | [99,102] |
| IL-18 | Together with IL-12, triggering IFN-γ and TNF-α action. In synergy with IL-12, inducing production of mitochondrial reactive oxygen species. | [99,102] |
| GM-CSF (CSF-2) | Contribution to classical activation of macrophages. Contribution to the recruitment of neutrophils and monocytes to the site of infection, and in mobilization of monocytes from bone marrow. Stimulation of production of MCP-1 by neutrophils and macrophages. Enhanced ADCC by neutrophils. Contribution in secretion of properdin leading to alternative pathway of complement activation. | [81,85,208,238] |
| HMGB-1 | Activation of neutrophil adhesive and migratory functions, and production of reactive oxygen species. Increased expression of ICAM-1 and VCAM-1. | [140,141,264,265,270] |
| IL-4 | Stimulation of production and secretion of IgG1 and IgE (IgE production inhibited by IL-8). Increased production of IL-6. Decreased expression of ICAM-1. | [188,190,196,197,294,295] |
| IL-15 | Development of NK cells and induction of their cytotoxicity. | [206] |
| IL-2 | Induction of NK cell proliferation. Induction of regulatory T cells to inhibit NK cell function. | [206,207] |
| IL-1 | Increased expression of ICAM-1 and VCAM-1. | [140,264,265,270] |