Chronic Inflammation and Metabolic Stress

Abstract

Macrophages are associated with various tissues and either derive from monocytes circulating in the blood or from self-renewing embryonal cell popula- tions. They show a large variety of stimulus- and tissue-specifi c functions, of which the extremes are pro-infl ammatory M1-type and anti-infl ammatory M2-type macro- phages. M1 macrophages are key cells in the initiation of the acute infl ammatory response, while M2 macrophages are resolving infl ammation and coordinate tissue repair. However, tissue infl ammation is not only caused by bacterial infection or tissue injury but may also derive from changes in the concentration of nutrients and metabolites. In this case, the immune system cannot cope the primary stimulus, so that chronic infl ammation develops. This metabolic stress, in contrast to infectious or traumatic stress, is often caused by lipid overload in the blood and in adipose tis- sue. This again is a hallmark of age-related metabolic diseases, such as obesity, insulin resistance and atherosclerosis. For example, hypercholesterolemia (Sect. 11.3 ) causes stress to macrophages and their associated cells. Moreover, perturba- tions of the homeostasis of nutrient metabolism dys-regulate functions of the liver.