Effects of local or systemic administration of meloxicam on mammary gland inflammatory responses to lipopolysaccharide-induced mastitis in dairy cows

Nonsteroidal anti-inflammatory drugs (NSAID) are commonly used in combination with antimicrobial mastitis treatments to reduce pain. Little is known about whether meloxicam, an NSAID designed for the preferential inhibition of cyclooxygenase-2 over cyclooxygenase-1, affects the mammary immune response. The objective of this study was to analyze the mammary immune response to intramammary (local) or intravenous (systemic) administration of meloxicam with or without immune activation by lipopolysaccharide (LPS). We challenged 108 quarters of 30 cows with or without a low or high dose of LPS from Escherichia coli (0.1 or 0.2 mu g/quarter), with or without meloxicam via intramarnrnary administration (50 mg/quarter) or intravenous injection (0.5 mg/kg of body weight; similar to 300 mg/cow). Intramarnrnary administration of meloxicam alone did not trigger an acute inflammatory response, verified by unchanged somatic cell count (SCC) and lactate dehydrogenase (LDH), BSA, and IgG concentrations in milk, which are normally augmented during mastitis due to an opening of the blood-milk barrier. Similarly, intramammary meloxicam did not change the mRNA abundance of inflammatory factors in mammary gland tissue. As expected, quarters challenged with either dose of LPS showed increased leukocyte infiltration (SCC); increased LDII, BSA, IgG, Na, and Cl concentrations; and diminished K concentrations in milk. In contrast to our hypothesis, the addition of intramammary or intravenous meloxicam did not reduce these markers of mastitis in milk. Instead, intramammary meloxicam appeared to accelerate the SCC response to LPS, but only at the lower LPS dose. Moreover, the mRNA expression of inflammatory factors in mammary tissue was not modified by the intramammary application of rneloxicarn compared with the con- tralateral quarters that were challenged with LPS only. We demonstrated for the first time that intramammary meloxicarn at a dose of 50 mg/quarter did riot trigger an immune response in the mammary glands of dairy cows. At the doses we used, meloxicam (intrarnammary or systemic) did not lower inflammatory responses. The intrarnammary administration of meloxicam seemed to stimulate leukocyte recruitment into the milk in quarters challenged with a low dose of LPS. The integrity of the blood-milk barrier was not protected by meloxicam in LPS-stimulated quarters. This study provides the first indications that meloxicarn does not limit the inflammatory response in the mammary gland, although it does not impair the mammary immune system.

Automated summary

This study found that meloxicam did not limit the inflammatory response in the mammary gland and did not impair the mammary immune system. Interestingly, intramammary meloxicam appeared to stimulate leukocyte recruitment into the milk in quarters challenged with a low dose of LPS.