The Effect of Lipopolysaccharide-Induced Experimental Bovine Mastitis on Clinical Parameters, Inflammatory Markers, and the Metabolome: A Kinetic Approach

Abstract

Mastitis is an inflammatory condition of the mammary tissue and represents a major problem for the dairy industry worldwide. The present study was undertaken to study how experimentally induced acute bovine mastitis affects inflammatory parameters and changes in the metabolome. To this end, we induced experimental mastitis in nine cows by intramammary infusion of 100 µg purified Escherichia coli lipopolysaccharide (LPS) followed by kinetic assessments of cytokine responses (by enzyme-linked immunosorbent assay), changes in the metabolome (assessed by nuclear magnetic resonance), clinical parameters (heat, local pain perception, redness, swelling, rectal temperature, clot formation, and color changes in the milk), and milk somatic cell counts, at several time points post LPS infusion. Intramammary LPS infusion induced clinical signs of mastitis, which started from 2 h post infusion and had returned to normal levels within 24–72 h. Milk changes were seen with a delay compared with the clinical signs and persisted for a longer time. In parallel, induction of IL-6 and TNF-α were seen in milk, and there was also a transient elevation of plasma IL-6 whereas plasma TNF-α was not significantly elevated. In addition, a robust increase in CCL2 was seen in the milk of LPS-infused cows, whereas G-CSF, CXCL1, and histamine in milk were unaffected. By using a metabolomics approach, a transient increase of plasma lactose was seen in LPS-induced cows. In plasma, significant reductions in ketone bodies (3-hydroxybutyrate and acetoacetate) and decreased levels of short-chain fatty acids, known to be major products released from the gut microbiota, were observed after LPS infusion; a profound reduction of plasma citrate was also seen. Intramammary LPS infusion also caused major changes in the milk metabolome, although with a delay in comparison with plasma, including a reduction of lactose. We conclude that the LPS-induced acute mastitis rapidly affects the plasma metabolome and cytokine induction with similar kinetics as the development of the clinical signs, whereas the corresponding effects in milk occurred with a delay.

Localized and Systemic Inflammatory Mediators in a Murine Acute Mastitis Model

“…Third, we cannot rule out the effect of time in our observations of cytokine levels in the plasma because our plasma cytokine analyses were conducted at 0 and 12 h of LPS treatment. However, the time effect should be minimal, as observed in other studies, 16 , 57 and unlikely to impact our major observations. Finally, our observations were limited to only one time point (12 h after LPS treatment).…”

Chronic Inflammatory Lameness Increases Cytokine Concentration in the Spinal Cord of Dairy Cows

“…Zhang et al (35) measured plasma TNF-α in transition cows before clinical signs of lameness, describing higher concentrations during the pre and postpartum, which suggested a state of clinical inflammation during that period. Similarly, Johnzon et al (36) described an increased in TNFα concentration both in plasma and milk after induction of mastitis in dairy cows. Although, the CSF concentration of TNF-α has not been reported in cows, our results are similar to those previously reported for human patients with chronic pain.…”

Houttuynia Essential Oil and its Self-Microemulsion Preparation Protect Against LPS-Induced Murine Mastitis by Restoring the Blood–Milk Barrier and Inhibiting Inflammation

“…MPO is a member of the heme peroxidase superfamily, and its expression level and activity can reflect the state of neutrophil infiltration (21,22). HEO and SME-HEO significantly reduced MPO expression in mammary gland tissue, and the efficacy of SME-HEO was better than that of HEO at corresponding doses.…”

“…The blood-milk barrier (BMB) plays an important role in mammary gland function, which is adversely affected if the integrity of the BMB is compromised (17,18). Studies have shown that lipopolysaccharide (LPS)-induced mastitis activates the MAPK and NF-kB signaling pathways (19)(20)(21)(22), resulting in the destruction of mammary tissue structure and damage to BMB integrity (23). Inhibiting the release of inflammatory factors in mammary gland tissue and protecting the integrity of the BMB may play an important role in the treatment of mastitis.…”