Comparison of inflammatory response and morphologic damage induced by endotoxin in mouse and bovine mammary gland

Pathogenic inflammation of the mammary gland, known as mastitis, wields an annual multi-billion dollar financial burden on American dairy farmers. Novel treatment and prevention options are of paramount interest in laboratories across the world. Researchers often employ the use of lipopolysaccharide (LPS) and murine models in their studies of bovine mastitis. While existing studies have identified individual inflammatory responses of the mouse and cow to LPS induced inflammation, there has been no direct comparison of the degree to which these immune responses correlate with each other. The focus of the present study was to identify similarities between the animal models, specifically in terms of inflammation-induced alveolar morphologic changes and local cytokine production. Ten multiparous cows and 18 virgin mice were selected for this study. In mice, the 4th inguinal mammary glands were unilaterally treated with either lipopolysaccharide (LPS) or PBS, and effects were measured at 12h and 24h. In cows, 5 control animals received an intramammary saline infusion in one half udder (CS), whereas a separate 5 treatment animals had one half udder infused with saline (TS) and the contralateral side infused with LPS (TL). The mammary glands were biopsied at 0h, 3h, and 12h, relative to the infusion. Assessments of alveolar morphology indicated that there were no significant changes to alveolar, lumen, or mammary epithelial cell (MEC) area between control and treatment groups, or across time, in either cow or mouse. There was a significant difference between treatment groups regarding MEC diameter in bovine tissue, but this significance was not applicable to specific time points. Cytokine analysis suggested rapid, local immune response as indicated by significant increases in the concentration of proinflammatory cytokines such as monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF-α) following LPS challenge in both mouse and cow (P \u3c 0.05). Significance was also detected regarding the interaction [5] between time and treatment for these cytokines in bovine samples (P \u3c 0.05), and a significant pattern emerged, indicating peak pro-inflammatory cytokine concentration at 3h in bovine samples. Additionally, systemic cytokine responses were implied by positive variations in IFN-γ, IL-4, and MCP-1 concentrations at 3h and 12h between CS and TS groups in bovine samples. Taken together, this data supports that the mouse may be a feasible model for studies of alveolar morphology and local cytokine proliferation in endotoxin-induced bovine mastitis