• Bacterial components such as lipopolysaccharides (LPS) can translocate from the uterus to the mammary gland.
• Repeated infusion of LPS into the uterus improves leukocyte function in mammary glands.
• Goats with enhanced leukocyte function show improved LPS clearance ability and, as a result, demonstrate a moderate inflammatory response to subsequent intramammary LPS administration.

Mastitis is an inflammatory disease of the mammary gland and one of the most common diseases in dairy cows. It is usually caused by bacterial infection that enters through the teat canal. A previous study found that repeated intrauterine infusion of lipopolysaccharide (LPS) for five consecutive days temporarily increased milk somatic cell counts (SCC; an inflammation indicator) but then decreased on the third day despite continued infusion. Suggesting that the mammary gland might develop "endotoxin tolerance (ET).” However, the specific changes in the mammary gland under ET remain unknown. Therefore, the aim of this study was to analyze the function of milk leukocytes under the LPS tolerance conditions.

To induce ET conditions, goats were infused with intrauterine LPS for three consecutive days. Subsequently, intramammary LPS infusion was performed to induce inflammation. The results showed that LPS-tolerant goats exhibited suppressed inflammatory responses to the intramammary LPS challenge. Furthermore, their milk leukocytes exhibited increased activation, as demonstrated by higher phagocytic activity and CD11b expression compared to the control group.

These findings suggest that repeated intrauterine LPS infusion induces tolerance in the mammary gland, improving leukocyte function, which leads to better bacterial clearance and reduced inflammation following subsequent intramammary LPS stimulation.

This study is expected to contribute to the development of novel therapeutic strategies for the treatment and control of inflammatory diseases. Although this study was conducted using a goat model, further studies are needed to explore how ET can be applied to reduce the damage caused by bacterial infections in dairy cows.

• Journal: Innate Immunity
• Title: Mammary leukocytes function of endotoxin tolerant goat induced by intrauterine infusion of lipopolysaccharide
• Authors: Jirapat Jaisue, Naoki Suzuki, Takahiro Nii, Naoki Isobe
• DOI: 10.1177/17534259251341659