Cell self-destruction (programmed cell death), immunonutrition and metabolism

Abstract

Immunologists have long been puzzled by the self-destructive nature of the inflammatory response. Inflammation can be elicited by various harmful stimuli, such as microbial/viral infections, allergic reactions, chemical insults, lipotoxicity, tissue damage, or other types of traumas. Breaking down damaged cells and converting them into various nutrients which are useful for tissue regeneration is among the most important functions of the human immune system in maintaining health. A localized inflammatory response is protective if the human immune system can effectively eliminate the harmful stimuli and initiate the healing process. Cell self-destruction (programmed cell death) includes phenomena of apoptosis, pyroptosis, necroptosis, necrosis and so on. Phagocytosis is employed to remove various cell debris produced by cell self-destruction and for conversion into nutrients. The immune system thus represents a powerful nutrient generator. At these moments, digestion and immunity are interrelated and integrated, playing the essential role of disease prevention and immunonutrition acquisition. In the event of microbial/viral infections, the nutritional flux produced by infected host cell self-destruction (inflammation) may be much greater than those produced by normal apoptosis, and may even be much greater than the nutrition provided by daily food intake. Thus, infection-induced inflammation may induce illness-associated anorexia to avoid overnutrition. When the nutrition generated by the degradation of infection-damaged cells exceeds the nutritional requirements of tissue regeneration, most excess nutrients will be converted into lipid intermediates. Lipid intermediates will invade healthy non-adipose tissue, leading to lipotoxicity and further tissue damage. In such a case, the main product (lipid intermediates) of the inflammatory response is also a strong harming stimulus for tissue/cell damage. This is amplified during the inflammatory response, forming a vicious cycle, making inflammatory response extremely destructive. The state of overnutrition will be exacerbated by the loss of lean body mass, coupled with excess lipid intermediate spillover into healthy tissues and organs, exacerbating the inflammatory response, which is characteristic of critically ill or injured patients and of most autoimmune diseases.