Mastitis is the most prevalent disease in dairy cattle worldwide and not only causes huge economic losses in the dairy industry but also threatens public health. To evaluate the therapeutic potential of melatonin in mastitis, we examined the ability of melatonin to protect bovine mammary epithelial cells (bMECs) from the harmful effects of lipopolysaccharide (LPS). We found that melatonin inhibited the LPS-binding protein–CD14–TLR4 signaling pathway in bMECs, which had opposing effects on pro-inflammatory and anti-inflammatory mediators. Melatonin decreased LPS-induced expression of pro-inflammatory cytokines, chemokines, and positive acute-phase proteins (APPs), including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, granulocyte-monocyte colony-stimulating factor, chemokine CC motif ligand (CCL)2, CCL5, serum amyloid A, haptoglobin, C-reactive protein, ceruloplasmin, and α-1 antitrypsin, and increased expression of the anti-inflammatory cytokine IL-1Ra and the negative APP fibrinogen. In addition, melatonin increased dityrosine levels but suppressed nitrite levels by upregulating the expression of Nrf2 and heme oxygenase-1 in the Nrf2 antioxidant defense pathway. Finally, melatonin administration increased the viability of LPS-stimulated bMECs. These results suggest that melatonin protects bMECs from LPS-induced inflammatory and oxidant stress damage and provide evidence that melatonin might have therapeutic utility in mastitis.

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The aim of the present study was to examine changes in innate immune factors in the milk of mastitic dairy cows treated with antibiotics. Cows in the antibiotics group (n = 13) were infused into the mammary gland with cefazolin on the sixth day after mastitis was diagnosed (the day of the mastitis diagnosis = day -6). The control group (n = 12) was not treated. Milk samples were collected once every 2 days from days -6 to 12 and somatic cell count (SCC), lingual antimicrobial peptide (LAP), and lactoferrin (LF) concentrations and lactoperoxidase (LPO) activity were measured. SCC and LF concentrations in the antibiotics group markedly decreased after the antibiotic treatment. When cows in the antibiotics group were divided according to SCC on day 0, LAP concentrations and LPO activity in cows with a lower SCC on day 0 (<5 × 10(6) cell/mL) were significantly higher and lower than those in cows with a higher SCC, respectively. These results suggest that LF concentration decreased with decrease in SCC after treatment and that LAP concentration and LPO activity differed depending on the severity of mastitis. This is the first report to reveal the dynamics of innate immune factor in milk of cows treated for clinical mastitis.

We investigated the production of staphylococcal enterotoxin (SE) with respect to coagulase types by methicillin-resistant Staphylococcus aureus (MRSA). A total of 138 strains of MRSA, which were isolated from clinical materials in the surgical ward between 1983 and 1990, were studied. Coagulase type IV strains produced SE A only, whereas coagulase type II strains were classified into four groups by SE production: SE B producing strains (32.7%), SE C producing strains (29.8%), SE B and C coproducing strains (12.5%), and SE A and C coproducing strains (25.0%). Almost all of the organisms (nine of ten) which were isolated from the feces of patients with MRSA enteritis were SE A and C coproducing strains. The coincidence in time of the prevalence of MRSA enteritis and the isolation SE A and C coproducing strains also demonstrated that these strains caused MRSA enteritis. Although SE C producing strains and SE A and C coproducing strains were simultaneously prevalent in 1990, the former tended to be sensitive while the latter tended to be resistant to minocycline. Considering the variety of antibiotic sensitivity in coagulase type II strains, it is thus considered to be of critical importance for epidemiologic purposes to further characterize isolates by SE typing.