Zootecnica International - World Poultry Journal

Elizabeth KOUTSOS
Animal Science Department
California Polytechnic State University
San Luis Obispo, CA
U.S.A.

Introduction

The immune system can be divided into two major categories, the innate and the acquired immune systems. The innate immune system consists of monocytes, macrophages, neutrophils/heterophils and other granulocytes (e.g., eosinophils, basophils). This portion of the immune system constitutes the first line of defense against pathogens and consists of recognition, leukocyte recruitment, phagocytosis and/or destruction of the antigen, followed by antigen presentation to other immune cells. The acquired immune system consists of B & T lymphocytes, dendritic cells, and macrophages, and this portion of the immune system is responsible for antibody-mediated defenses, anti-viral and anti-cancer responses, and memory of previous exposures.
A major component of the innate immune response is the inflammatory response, which is directed by several cytokines including interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) and IL-6. These “pro-inflammatory” cytokines serve as communication molecules for the immune system, and are responsible for many of the alterations in nutritional status that occur during an immune response. In fact, it is often the reduced performance associated with the inflammatory response that is most costly in animal production systems, rather than the actual “cost” of mounting the immune response. For this reason, preventing exposure to pathogens through practices such as biosecurity programs, vaccination schedules, and feeding of antibiotics, probiotics or other compounds that can modulate gut microflora populations can prevent the onset of the immune response in the first place.
Additionally, an understanding of the immune system and it’s interactions with the nutrition of an animal can allow for optimal diet formulation before, during and after a disease challenge. This type of strategy can help to maximize the effectiveness of an immune response to invading pathogens, while minimizing the deleterious effects of an immune response on the host.

Effects of an immune response on nutrition

The inflammatory response and its pro-inflammatory cytokine mediators direct many concerted changes in the nutritional status of an animal, including altered nutrient partitioning and metabolism, reduced food intake and reduced growth and performance. In fact, the reduction in food intake that accompanies an inflammatory response is responsible for ~70% of the decrease in animal growth, and the remaining 30% reduction in growth is due to inefficiencies in nutrient absorption and metabolism (Klasing et al., 1987). Therefore, preventing this response is the producer’s best option to maintain animal performance.
The inflammatory response has profound effects on the hormonal profile of an animal, and generally decreases anabolic hormones such as growth hormone (GH) (Elsasser et al., 1997) and insulin-like growth factor 1 (IGF-1) (Elsasser et al., 1995), and increases the release of catabolic hormones such as glucocorticoid (Elsasser et al., 2000). At the same time, a reduction in food intake also leads to reduced IGF-1 levels, leading to catabolism of skeletal muscle. This change in hormonal milieu promotes catabolism, which is in direct contrast to the goals of animal production systems.
Often overlooked, the pathology associated with a disease challenge can have significant metabolic and nutritional consequences. For example, intestinal pathogens may cause significant damage to the gut mucosa, thereby reducing nutrient absorption and enhancing blood loss (also directing nutrients away from the body). These pathogen-induced metabolic derangements must be included when calculating the nutritional costs of mounting an immune response.
Finally, in addition to indirect effects of immune responses on nutritional status (i.e., reductions in food and nutrient intake, pathogen damage, alterations in hormonal profiles), the immune response directly affects nutrient partitioning and metabolism. Energy metabolism and substrate use are significantly altered by inflammatory responses. For example, inflammation increases rates of glucose oxidation and gluconeogenesis, and increases hepatic triacylglycerol synthesis from fatty acids released from adipose (Beisel, 1977). Thus, energy substrates like glucose and fatty acids are involved in “futile cycling,” rather than productive purposes. Additionally, TNF-α induces insulin resistance by interfering with insulin receptor signaling, which affects glucose and amino acid uptake in peripheral tissues by their insulin-sensitive transporters (Hotamisligil et al., 1994).
The inflammatory response generally repartitions nutrients to the liver for production and secretion of a number of proteins, called acute phase proteins. This redirection of nutrients results in less lean tissue accretion and more adipose and viscera accretion compared to unchallenged birds (Benson et al., 1993). Therefore, amino acids that would normally be directed to the skeletal muscle for protein accretion, are instead partitioned to the liver (Klasing, 1988; Bistrian et al., 1992). In total, 6.7% of dietary lysine is used to support the immune response during an inflammatory challenge, and most of this is used for synthesis of acute phase proteins. However, while the immune system increases lysine utilization during an inflammatory challenge, the overall requirement of lysine for growth decreases in growing pigs and chickens, presumably due to a decrease in lysine utilization for muscle accretion that outweighs the increases needed for the anabolic processes of the immune response (Klasing and Barnes, 1988; Williams et al., 1997; Williams et al., 1997; Williams et al., 1997; Webel et al., 1998).
Mineral nutrition of an animal is also affected by inflammatory responses. For example, the efficiency of iron absorption is greatly diminished during an inflammatory response in order to prevent pathogens from obtaining this limiting nutrient (Weinberg, 1974; Weinberg, 1999). Plasma zinc levels are also reduced by an immune response, as a result of increased liver metallothionein production (Hallquist and Klasing, 1994), for which zinc serves as a co-factor. Water absorption is significantly reduced by sepsis (Kanno et al., 1996), as is sodium, chloride and glucose absorption, and flux of these nutrients is often directed out of the body. Calcium metabolism is altered such that bone mineral density is reduced, while blood calcium levels are elevated (see review by (Raisz, 1999). The biological basis for this change has been hypothesized to be increased surveillance of bone tissue, although experimental evidence is currently lacking.
Vitamin nutrition is also modified by an inflammatory response. Activation of the immune system results in the generation of reactive oxygen species (ROS). Antioxidants such as ascorbic acid and α-tocopherol protect macromolecules and host cells against damage from these ROS, and the requirements for antioxidant nutrients seems to be greater for animals undergoing an inflammatory challenge as compared to healthy animals (Webel et al., 1998; Yoshida et al., 1999). However, as previously stated, the level of nutrient intake is decreased during an immune response. Therefore, it will likely be much more effective to increase antioxidant intake prior to a disease challenge or vaccination, or to make appropriate changes in the diet to account for reduced feed consumption. Changes in vitamin A metabolism are also apparent during disease challenges. Synthesis of the vitamin A transport protein, retinol-binding protein (RBP), is dramatically reduced during an immune response (Rosales et al., 1996; Rosales and Ross, 1998). The primary consequence of reduced RBP synthesis is that stored vitamin A cannot be transported to extra-hepatic tissues, and consequently plasma vitamin A levels are significantly reduced by disease.
Finally, partitioning of nutrients that are not considered essential is also altered by disease challenge. In birds, viral, bacterial and parasite challenges are associated with reductions in carotenoid-based pigmentation (Squibb et al., 1955; Squibb et al., 1971; Allen, 1992; Koutsos et al., 2003). These changes may be a result of reduced dietary absorption and increased losses through intestinal bleeding (e.g. intestinal parasites such as coccidia, (Allen, 1992), or a by-product of altered lipid metabolism. Since many carotenoids are transported with lipoprotein particles, changes in lipoprotein synthesis and uptake may play a significant role in carotenoid partitioning during an immune response. Finally, as is the case with vitamin E, carotenoids may play a functional role in immune responses, given their antioxidant potential and other immunomodulatory functions, and thus may be metabolized at a greater rate during an immune response.

Conclusions

An understanding of the interactions between nutrition and immunity are essential for improving animal welfare and production. In general, inflammatory responses reduce feed intake, which accounts for a majority of the reductions in growth rate seen during disease challenges. The use of nutrients for growth is reduced, while the liver increases acute phase protein synthesis, which accounts for reductions in lean muscle mass during inflammation. Some nutrients are sequestered to prevent their acquisition by bacteria, and the most notable of these nutrients is iron. Some nutrients are used in greater quantities during inflammation, including antioxidant nutrients such as Vitamin E. Finally, some nutrients have altered metabolism, while the function of these changes remains unclear. What is clear is that prevention of the disease challenge is the best mechanism by which a producer can ensure good performance. Additionally, optimal nutrition before and after a challenge can help to minimize the economic consequences of the inflammatory response.


References are available on request.
From Proceedings of the “Midwest Poultry Federation Convention”, St. Paul,