Invited review: The influence of immune activation on transition cow health and performance-A critical evaluation of traditional dogmas.

The progression from gestation into lactation represents the transition period, and it is accompanied by marked physiological, metabolic, and inflammatory adjustments. The entire lactation and a cow's opportunity to have an additional lactation are heavily dependent on how successfully she adapts during the periparturient period. Additionally, a disproportionate amount of health care and culling occurs early following parturition. Thus, lactation maladaptation has been a heavily researched area of dairy science for more than 50 yr. It was traditionally thought that excessive adipose tissue mobilization in large part dictated transition period success. Further, the magnitude of hypocalcemia has also been assumed to partly control whether a cow effectively navigates the first few months of lactation. The canon became that adipose tissue released nonesterified fatty acids (NEFA) and the resulting hepatic-derived ketones coupled with hypocalcemia lead to immune suppression, which is responsible for transition disorders (e.g., mastitis, metritis, retained placenta, poor fertility). In other words, the dogma evolved that these metabolites and hypocalcemia were causal to transition cow problems and that large efforts should be enlisted to prevent increased NEFA, hyperketonemia, and subclinical hypocalcemia. However, despite intensive academic and industry focus, the periparturient period remains a large hurdle to animal welfare, farm profitability, and dairy sustainability. Thus, it stands to reason that there are alternative explanations to periparturient failures. Recently, it has become firmly established that immune activation and the ipso facto inflammatory response are a normal component of transition cow biology. The origin of immune activation likely stems from the mammary gland, tissue trauma during parturition, and the gastrointestinal tract. If inflammation becomes pathological, it reduces feed intake and causes hypocalcemia. Our tenet is that immune system utilization of glucose and its induction of hypophagia are responsible for the extensive increase in NEFA and ketones, and this explains why they (and the severity of hypocalcemia) are correlated with poor health, production, and reproduction outcomes. In this review, we argue that changes in circulating NEFA, ketones, and calcium are simply reflective of either (1) normal homeorhetic adjustments that healthy, high-producing cows use to prioritize milk synthesis or (2) the consequence of immune activation and its sequelae.