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

Abstract

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 µg/quarter), with or without meloxicam via intramammary administration (50 mg/quarter) or intravenous injection (0.5 mg/kg of body weight; ~300 mg/cow). Intramammary 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 LDH, 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 meloxicam compared with the con-tralateral quarters that were challenged with LPS only. We demonstrated for the first time that intramammary meloxicam at a dose of 50 mg/quarter did not trigger an immune response in the mammary glands of dairy cows. At the doses we used, meloxicam (intramammary or systemic) did not lower inflammatory responses. The intramammary 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 meloxicam does not limit the inflammatory response in the mammary gland, although it does not impair the mammary immune system.

Flunixin Meglumine Reduces Milk Isoprostane Concentrations in Holstein Dairy Cattle Suffering from Acute Coliform Mastitis

“…Additional NSAIDs are currently being examined to improve inflammatory responses and milk production during mastitis and onset of lactation. However, inhibition of proper inflammatory function [ 60 ] and lack of effect on haptoglobin concentrations [ 61 ] further highlight the need for improved markers of inflammation and anti-inflammatory treatment. A better understanding of the inflammatory state of cows at the time of NSAID treatment has the potential to improve the clinical outcomes of severe coliform mastitis with systemic involvement.…”

Effect of 2% meloxicam injection in Holstein dairy cows on acute clinical mastitis without systemic symptoms

“…compared the changes in milk SCC in cows that were experimentally injected with intramammarily LPS and intravenously injected with MX to those injected with intramammarily LPS alone. Their results showed that MX did not significantly decrease SCC, with similar values 9 hr after injection [ 3 ]. They also reported that injecting MX alone into the udder did not affect SCC [ 3 ].…”

“…Their results showed that MX did not significantly decrease SCC, with similar values 9 hr after injection [ 3 ]. They also reported that injecting MX alone into the udder did not affect SCC [ 3 ]. In the present study, the LS for both groups were significantly lower ( P <0.01) on days 0 and 1 compared to day 3.…”

Invited review: The role of the blood–milk barrier and its manipulation for the efficacy of the mammary immune response and milk production

“…This response was different than 50 mg of intramammary ketoprofen, which limited the leukocyte infiltration after LPS challenge (Dan et al, 2018). In contrast, meloxicam promoted an earlier increase in SCC response when the mammary gland immune system was stimulated with a low dose of LPS (Caldeira et al, 2021). Other NSAID such as the nonselective diclofenac or the COX2-selective celecoxib impaired the mammary epithelial barrier in vitro by damaging the cells (Sintes et al, 2020).…”