Infectious disease detracts from farm profitability through decreased production efficiency and increased morbidity and mortality. Infections of the mammary gland (mastitis) or uterus (metritis) are common sources of inflammation in lactating cows, particularly during the periparturient period. Other health disorders common during this period (e.g., milk fever and ketosis) do not arise from infectious organisms, but instead have metabolic origins. Although the etiologies of infectious and metabolic disorders differ, epidemiologists report a significant association between their occurrences. For example, Curtis et al. (1985) reported that cows with milk fever were more than 5 times as likely to contract clinical mastitis as animals without milk fever. These results do not imply cause and effect; however, they suggest an association between the occurrences of one disease with that of a second disorder. Potential causal relationships between periparturient metabolism and immune function have been investigated for about the last 20 years, but this research has intensified recently.

Immunosuppression: An Interaction between Metabolism and Immunophysiology?

Part of the reason for the increased number and severity of infections around the time of calving is due to a weakened immune system, often termed as immunosuppression. This immune dysfunction is not limited to isolated immune variables; rather it is broad in scope and affects multiple functions of various immune cell types (Sordillo and Streicher, 2002). The combined results of these dysfunctions are that cows may be hyposensitive and hyporesponsive to antigens, and therefore more susceptible to infectious disease such as mastitis during the periparturient period (Mallard et al., 1998). Grommers et al. (1989) reported that fewer mammary quarters responded to low-dose E. coli endotoxin, and maximum somatic cell count also was somewhat later and less pronounced during early lactation than during mid-lactation. Furthermore, when live E. coli were administered into the mammary gland, periparturient cows experienced more rapid bacterial growth, higher peak bacterial concentration, higher fever, and equal or greater proinflammatory cytokine concentrations in foremilk than did midlactation cows (Shuster et al., 1996).

Research results from our laboratory are in agreement with this decreased immune function around the time of calving and perhaps give some insights into which mechanisms may be impaired. Neutrophils (PMN) are recognized as being one of the most important cell types in protecting of the mammary gland and uterus from infection (Paape et al., 2002). We isolated PMN from midlactation (220-350 DIM and 100-200 d of gestation, n = 9), prepartum (12 d prior to calving, n = 8), and postpartum (7 DIM, n = 8) cows and studied various functional activities of these cells. The PMN from postpartum cows produced fewer intracellular (data not shown), extracellular (data not shown), and total reactive oxygen species (ROS). These ROS are compounds such as hydrogen peroxide that kill bacteria upon contact. Production of these ROS is part of how the immune system works to fight infection. This postpartum decrease in ROS expression is in agreement with other reports (Mehrzad et al., 2001) and could contribute to the attenuated pathogen killing capacity that has been reported after calving (Dosogne et al., 2001). A novel finding from our lab relates to the ability of PMN to produce neutrophil extracellular traps (NETs). These bacteriocidal structures were first reported by Brinkmann et al. (2004) and were subsequently reported to be expressed at similar levels in milk and blood (Lippolis et al., 2006), contrary to other antimicrobial mechanisms. Using the same experimental design as above for the ROS production, we reported (Revelo and Waldron, 2010) that PMN NETs expression is increased in PMN incubations isolated from cows 12 d prepartum, compared to PMN from postpartum or midlactation cows. This finding, along with the expression of NETs in milk (Lippolis et al., 2006), suggests that NETs expression by PMN is an important protective mechanism for the mammary gland of transition cows.

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