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The body’s reaction to critical illness, whether from infection, surgery, or trauma, is complex and multifactorial, and survival from an insult requires the successful coordination of responses to the stress of illness. A functional immune system is essential for survival, but an appropriate balance between the pro-inflammatory and anti-inflammatory responses must be maintained. It has long been known that baseline nutritional status has effects on inflammation, oxidative status, and immune function. More recently, however, providing specific nutrients to manipulate the immune system independent of caloric or macronutrient requirements for nutrition per se has evolved as a therapeutic modality. This is the basis for what has come to be known as immunonutrition.


The immune system is the body’s secondary defense against invasion, after skin and mucosal barriers, and is required for healing and repair after injury. Generally, this is a protective response, evolved over generations and across species, resulting in the systemic inflammatory response that is designed to make the environment of the body inhospitable for pathogens. This response in itself, however, can be overly exuberant and is primarily responsible for the multiorgan dysfunction that is commonly seen in the critically ill. With improved survival from initial insults and the organ dysfunction that follows, the balance shifts within several days to a more anti-inflammatory response, termed the compensatory anti-inflammatory response syndrome (CARS). Ultimately, if homeostasis is not restored, prolonged organ dysfunction results.1

The components of the immune system can be divided into 2 separate but well-integrated and interdependent groups. The first includes cells designed as first defenders that initiate the inflammatory response, comprising the innate immune system, while the second group is composed of cells that modulate the immune response and ultimately provide immune memory, known as the adaptive immune system. These groups act in concert to respond to injury and invasion by pathogens. Both are affected by baseline nutritional status and can be modulated by macro- and micronutrients.

Innate Immunity

The innate immune system is composed of cells that can respond to initial injury or pathogen invasion, inciting the inflammatory cascade within hours to days. These are monocytes, macrophages, polymorphonuclear (PMN) cells, dendritic cells, and natural killer (NK) cells. They can recognize pathogens upon initial contact via constitutively expressed cell surface receptors. They also function as phagocytes, which may directly kill pathogens intracellularly and/or digest proteins into antigenic peptides that are subsequently presented on the cell surface. The cell surface protein–antigen complex is recognized by lymphocytes, activating the adaptive immune system. Innate immune cells also secrete chemokines, which function as chemical attractants to other immune cells, and cytokines, which affect the function of other cells, such as lymphocytes, monocytes, and macrophages.

The cytokines and chemokines expressed by innate immune cells have both pro- and anti-inflammatory properties. Cytokines that are generally pro-inflammatory are interleukin ...

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