Effect of Carprofen Treatment Following Experimentally Induced Escherichia coli Mastitis in Primiparous Cows

Abstract

Acute Escherichia coli mastitis is one of the major sources of economic loss in the dairy industry due to reduced milk production, treatment costs, discarded milk, and occasional fatal disease. Nonsteroidal antiinflammatory drugs (NSAIDs) are frequently used as adjunctive therapy to antibiotics. The objective of the current study was to evaluate the effect of carprofen treatment following infusion of Escherichia coli into the mammary glands of primiparous cows during the periparturient period. Severity of mastitis was scored based on the average milk production in the uninfected quarters on d +2 postinoculation and a clinical severity score. Carprofen was administered intravenously at 9 h postchallenge, when clinical signs of mastitis appeared. In previous work, efficacy of NSAIDs was mainly evaluated using clinical symptoms. In the present study, the effect of carprofen on innate immune response was also assessed by quantification of inflammatory mediators. All primiparous cows reacted as moderate responders throughout the experimental period. Primiparous cows were intramammarily inoculated with 1 × 10 4 cfu of E. coli P4:O32 in 2 left quarters. Analysis of blood and milk parameters, including IL-8, complement component C5a, lipopolysaccharide-binding protein (LBP), soluble CD14, prostaglandin E 2 , and thromboxane B 2 was performed from d 0 to d +6 relative to intramammary inoculation. Rectal temperature in carprofen-treated animals was lower than in control animals at 3 and 6 h posttreatment. Treatment also restored the decreased reticulorumen motility that occurs during E. coli mastitis to preinfection levels faster than in control animals. Carprofen treatment resulted 2361in an earlier normalization of the clinical severity score. Eicosanoid (prostaglandin E 2 and thromboxane B 2 ) production in milk tended to be inhibited by carprofen. No significant differences in the kinetic patterns of somatic cell count, IL-8, complement component C5a, LBP, and soluble CD14 were observed. In conclusion, carprofen treatment improved general clinical condition by effective antipyrexia and restoration of reticulorumen motility but did not significantly inhibit eicosanoid production. Carprofen treatment did not result in a significant decrease of chemotactic inflammatory mediators, IL-8 and C5a, and early innate immune molecules, sCD14 and LBP. Therefore, major modulatory effects from NSAID administration were not observed in this mastitis model, although a larger study might confirm some apparent trends obtained in the present results. (Key words: primiparous cow, carprofen, Escherichia coli mastitis, moderate inflammation) Abbreviation key: C5a = complement component 5a, COX = cyclo-oxygenase, HR = heart rate, LBP = LPSbinding protein, NSAID = nonsteroidal anti-inflammatory drug, PGE 2 = prostaglandin E 2 , PIH = postinfusion hour, RT = rectal temperature, sCD14 = soluble CD14, TMB = tetramethylbenzidine, TXB 2 = thromboxane B 2 .

GROWTH AND DEVELOPMENT SYMPOSIUM: Inflammation: Role in the etiology and pathophysiology of clinical mastitis in dairy cows1

“…Pharmacological strategies to reduce the production of inftammatory mediators produced via the cyclooxygenase and lipoxygenase pathways have been studied extensively (Burvenich and Peeters, 1982;Anderson et al, 1986;Burvenich et al, 1989;Lohuis et al, 1989Lohuis et al, , 1991Rose et al, 1991;DeGraves and Anderson, 1993;Shpigel et al, 1994;Vangroenweghe et al, 2005;Banting et al, 2008). In those studies, pharmacological doses of nonsteroidal antiinftammatory dmgs were given either before the inftammatory challenge or at the onset of clinical signs of disease.…”

Invited review: Inflammation during the transition to lactation: New adventures with an old flame

“…One intriguing finding was that meloxicam treatment during mastitis decreased the risk of removal from the herd by 58% in the 45 wk following treatment (McDougall et al, 2009). Carprofen was shown to partially alleviate the decrease in ruminal contractions during mastitis (Vangroenweghe et al, 2005), which could help prevent a subsequent displaced abomasum. Similarly, meloxicam administration 1 d after assisted calving increased time spent eating in the subsequent 24 h (Newby et al, 2013).…”

Lipopolysaccharides, cytokines, and nitric oxide affect secretion of prostaglandins and leukotrienes by bovine mammary gland during experimentally induced mastitis in vivo and in vitro

“…Similar to the results from the caudal vena cava, PGE 2 concentration was increased by TNF and IL-1a infusions. Pezeshki et al [10] and Vangroenweghe et al [42] suggested that PGE 2 concentration in milk increased after intramammary challenge of E coli, and this PG production was related to bacterial growth and level of inflammatory response. Considering PGFM, all examined factors promoted its secretion, with exception of IL-1a.…”