Factors associated with concentrations of select cytokine and acute phase proteins in dairy cows with naturally occurring clinical mastitis

The objective of the current observational study was to determine the potential associations between cow factors, clinical mastitis (CM) etiology, and concentrations of select acute phase proteins and cytokines in milk from affected quarters of cows with CM. Cows with CM (n = 197) were grouped based on systemic disease severity, milk culture result, parity, days in milk (DIM), previous CM occurrence, and season of the year when CM occurred. Concentrations of lipopolysaccharide-binding protein (LBP), haptoglobin (Hp), BSA, IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-8, IL-10, IL-12, transforming growth factor (TGF)-alpha, and TGF-beta and activity of lactate dehydrogenase (LDH) were evaluated. Differences in the least squares means log(10) transformed concentrations of these proteins were compared using multiple linear regression mixed models. The milk concentrations of LBP, Hp, IL-1 beta, IL-10, and IL-12, and activity of LDH in milk were higher in cows with moderate to severe versus mild systemic disease. The concentrations of Hp, BSA, IL-1 beta, and IL-10 in milk were higher in cows with a gram-negative versus gram-positive milk culture result. Season of the year when CM occurred was associated with the concentration of all proteins evaluated except for IL-1 beta and IL-12. Concentrations were higher in the winter versus summer except for Hp and TGF-beta, for which the opposite was true. Concentrations of LBP, IL-10, and IL-12, and LDH activity in milk were associated with DIM group. Except for LBP, these proteins were lower in cows with CM during the first 60 DIM versus those in mid or later lactation. Interferon-gamma, TNF-alpha, and IL-8 were undetectable in 67, 31, and 20% of samples, respectively. Detection of IFN-gamma and IL-8 was associated with season, and detection of TNF-alpha and IL-8 was associated with systemic disease severity. The current study provides the most comprehensive report of milk concentrations of innate immune response proteins in cows with naturally occurring CM and identifies factors that potentially influence those concentrations. Further investigation into the seasonal variation of cytokine production and its potential effect on the outcome of CM is warranted. Furthermore, the results of this study provide useful data for planning future studies examining the role of the innate immune response in CM.