Metabolic and Physiological Ramifications of Immune Activation

Abstract Text: Activation of the immune system by bacterial and viral pathogens elicits a coordinated set of metabolic, physiological, and behavioral events, all of which result in reduced animal growth. During an acute infection, proinflammatory cytokines [e.g., tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1)] are produced by activated monocytes and macrophages in peripheral tissues, and these proteins serve as central mediators to induce coordinated events through mechanisms in the brain. Collectively referred to as ‘sickness behavior’, the non-specific symptoms of infection include fever, fatigue, alteration of sleep patterns, social isolation, decreased food and water intake, and weight loss. Beyond the outward signs of clinical infection, animals experience a repartitioning of body nutrients (especially amino acids and some minerals) designed to support the immune response while making the host environment incompatible with pathogen survival. A major challenges for nutritionists is that nutrient priorities are first for maintenance and second for growth (i.e,. lean tissue accretion), and maintenance requirements for energy and specific nutrients are elevated during an active infection, which reduces availability of nutrients for growth. For example, the febrile response harnesses metabolic inefficiency to produce heat and raise the core body temperature, while production of cytokines and immune cells requires significant resources (e.g., amino acids) to allow the host to mount an effective immune response. Thus, from a nutritional perspective, managing sick pigs involves delivery of nutrient profiles that support an appropriate level of immune reactivity while minimizing growth depression, and this must occur while the pig is experiencing a reduction in voluntary feed intake. Finding ways to manage the magnitude and duration of an acute inflammatory response is key to maximizing productive performance and profitability, but eliminating the proinflammatory response altogether is not an option because it is an important part of host immune defenses. Current evidence suggests that genetic selection for growth potential may negatively affect the ability for animals to cope with an infection, but this effect is likely most pronounced when animals are exposed to dietary nutrient deficiencies. To that end, a significant gap in knowledge exists regarding how to optimize nutrient profiles before and during an active infection. The classic nutritional approach has been the addition of specific nutrients or bioactive compounds to elicit immunomodulatory effects, but significant progress in this area is more likely to occur using a ‘systems’ approach to better understand the interaction of nutrition and immunology.

Keywords: immunology, metabolism, pig