Recognition by macrophages, other sentinel cells in tissues
Mediators (amines, cytokines)
Recruitment of leukocytes
Vasodilation,
EliminationEdema of microbes,
Cytokines,
Fig. 3.1 Sequence of events in an inflammatory reaction. Macrophages and other cells in tissues recognize microbes and damaged cells and  liberate mediators, which trigger the vascular and cellular reactions of inflammation. Recruitment of plasma proteins from the blood is not shown.
of inflammation that is called chronic inflammation. As discussed later in this chapter, chronic inflammation may follow acute inflammation or arise de novo. It is of longer duration and is associated with more tissue destruction, the presence of lymphocytes and macrophages, the proliferation of blood vessels, and fibrosis.
Inflammation is induced by chemical mediators that are produced by host cells in response to injurious stimuli. When a microbe enters a tissue or the tissue is
Table 3.1 Features of Acute and Chronic Inflammation injured, the presence of the infection or damage is sensed by resident cells, including macrophages, dendritic cells, mast cells, and other cell types. These cells secrete molecules (cytokines and other mediators) that induce and regulate the subsequent inflammatory response. Inflammatory mediators are also produced from plasma proteins that react to the microbes or to products of necrotic cells. Some of these mediators promote the efflux of plasma  and the recruitment of circulating leukocytes to the site where the offending agent is located. Mediators also activate the recruited leukocytes, enhancing their ability to destroy and remove the offending agent. Understanding the role of chemical mediators is important because most anti-inflammatory drugs target specific mediators. We shall discuss the mediators of inflammation in detail later, after we review the main steps in inflammatory reactions.
The external manifestations of inflammation, often called its cardinal signs, are heat (calor in Latin), redness (rubor), swelling (tumor), pain (dolor), and loss of function (functio laesa). The first four of these were described more than 2000 years ago by a Roman encyclopedist named Celsus, who wrote the then-famous text De Medicina, and the fifth was added in the late 19th century by Rudolf Virchow, known as the “father of modern pathology.” These manifestations occur as consequences of the vascular changes and leukocyte recruitment and activation, as will be evident from the discussion that follows.
Although normally protective, in some situations, the inflammatory reaction becomes the cause of disease, and the damage it produces is its dominant feature. For example, inflammatory reactions to infections are often accompanied by local tissue damage and its associated signs and symptoms (e.g., pain and functional impairment). Typically, however, these harmful consequences are self-limited and resolve as the inflammation abates, leaving little or no permanent damage. In contrast, there are many diseases in which the inflammatory reaction is misdirected (e.g., against self tissues in autoimmune diseases), occurs against normally harmless environmental substances that evoke an immune response (e.g., in allergies), or is excessively prolonged (e.g., in infections by microbes that resist eradication).