Inflammation and Transition Cow Disorders

The multitude of disorders that dairy cows face during the transition to lactation is a perennial source of concern for dairy producers, nutritionists, and veterinarians. Total disease incidence in the several weeks after parturition accounts for a substantial proportion of all morbidity on many dairies (Ingvartsen, 2006), with particularly high rates of  mastitis, metritis, milk fever, displaced abomasum, ketosis, and fatty liver, among other problems. Not surprisingly, these issues have been the focus of much research in recent decades. During that time, substantial progress has been made in some areas (e.g., milk fever); however, incidence of other disorders (e.g., displaced abomasum) may be on the rise (Goff, 2006).

It is well documented that cows suffering from one transition disorder are at greater risk for contracting others, including such seemingly unrelated conditions as mastitis and ketosis (Goff, 2006). The transition from gestation to lactation dramatically increases requirements for energy, glucose, amino acids, and other nutrients in dairy cattle. Simultaneously, feed intake is often depressed. The resulting negative energy balance suppresses immune function and promotes metabolic disorders, potentially explaining relationships between infectious and noninfectious transition disorders.

The most widely adopted practice to avoid metabolic disorders is the nutritional management of prepartum cows to prevent excess body condition. By limiting the pool of stored fat available for mobilization, restricting energy intake during the far-off dry period limits the increase in plasma non-esterified fatty acid (NEFA) concentrations during the transition period, resulting in lower fat storage and ketone production in the liver (Murondoti et al., 2004; NRC, 2001). However, results of controlled trials have been inconsistent with regard to nutritional management of dry cows; some studies have demonstrated a benefit from increased prepartum energy intake when body condition was not affected (Doepel et al., 2002), whereas restricting intake, even without affecting body condition, led to more favorable outcomes in other studies (Holcomb et al., 2001). These inconsistencies suggest that our understanding of metabolic disorders remains incomplete.

Recent research has highlighted the role of inflammation in infectious diseases and has suggested that inflammation is involved in metabolic diseases as well. A key role for inflammation in numerous transition cow disorders may help to explain links between these diverse conditions and may also improve our ability to predict and prevent metabolic problems in transition cows. This presentation will provide an overview of findings relating to the role of inflammation in transition disorders and provide recommendations to smooth the transition to lactation.

Please check this link first if you are interested in organic or specialty dairy production.
Inflammatory Responses to Infection

During infections such as mastitis or metritis, immune cells in the body recognize invading pathogens and become activated. When the infection is caused by Gram-negative bacteria, endotoxin released by the bacteria also activates immune cells. The activation of local and systemic host defense mechanisms requires cross-talk between numerous types of immune cells. One component of this response is inflammation. The host of signaling molecules released by activated immune cells includes inflammatory mediators such as nitric oxide, prostaglandins, and cytokines. While many of these molecules promote local inflammation and increased blood flow, inflammatory cytokines play a key role in stimulating systemic inflammatory responses, including increased body temperature, increased heart rate, and decreased feed intake (Dantzer and Kelley, 2007). Cytokines are able to alter many physiological systems because nearly all cell types express cytokine receptors. Key inflammatory cytokines include tumor necrosis factor alpha (TNFα), interleukin 1β, and interleukin 6; these inflammatory cytokines act through many of the same signaling cascades and often produce similar responses in cells.

One effect of cytokines is to activate production of acute phase proteins. Primarily produced by the liver, this class of proteins includes haptoglobin, serum amyloid A, and C-reactive protein. Proteins that participate in the acute phase response to infection are generally found in very low abundance in the bloodstream but are greatly elevated during systemic activation of the immune system. The importance of acute phase proteins in the response to infection is somewhat unclear, but they have gained widespread acceptance as markers of inflammation (Petersen et al., 2004). Other proteins are known as negative acute phase proteins because their concentrations decline dramatically during the acute phase response.

It is clear that mammary and uterine infections result in both local and systemic inflammation. Coliform mastitis results in release of endotoxin into the bloodstream and increased plasma concentrations of cytokines and acute phase proteins (Hoeben et al., 2000). Likewise, metritis is associated with an acute phase response in transition cows (Huzzey et al., 2009); in fact, plasma haptoglobin is elevated prior to clinical signs of metritis.
Is There a Role for Inflammation in Metabolic Disorders as Well?

Inflammation has been proposed as a missing link in the pathology of metabolic disorders in transition cows (Drackley, 1999). The metabolic effects of acute systemic inflammation include adipose tissue mobilization, breakdown of liver glycogen, and liver triglyceride accumulation, all of which occur during the transition period. More specifically, cytokines promote the breakdown of fat stores through decreased feed intake (Kushibiki et al., 2003), impaired insulin sensitivity, and direct stimulation of lipolysis (Kushibiki et al., 2001). All of these conditions are associated with ketosis and fatty liver in dairy cattle (Ingvartsen, 2006). Even more intriguing is the evidence that TNFα decreases liver glucose production (Kettelhut et al., 1987) and promotes triglyceride accumulation once mobilized NEFA reach the liver (García-Ruiz et al., 2006). The direct effects of cytokines on liver metabolism may play a key role in promoting metabolic disorders in transition cows, especially those already combating infectious disorders or with excessive body condition.