In this discussion of acute inflammation, we emphasize the importance of neutrophils and macrophages. However, it has become clear that some T lymphocytes, which are cells of adaptive immunity, also contribute to acute inflammation. The most important of these cells are those that produce the cytokine IL-17 (so-called “TH17 cells”), which are discussed in more detail in Chapter 5. IL-17 induces the secretion of chemokines that recruit other leukocytes. In the absence of effective TH17 responses, individuals are susceptible to fungal and bacterial infections, and the skin abscesses that develop are “cold abscesses,” lacking the classic features of acute inflammation, such as warmth and redness.
Termination of the Acute Inflammatory Response
Such a powerful system of host defense, with its inherent capacity to cause tissue injury, needs tight controls to minimize damage. In part, inflammation declines after the offending agents are removed simply because the mediators of inflammation are produced in rapid bursts, only as long as the stimulus persists, have short half-lives, and are degraded after their release. Neutrophils also have short half-lives in tissues and die by apoptosis within hours to a day or two after leaving the blood. In addition, as inflammation develops, the process itself triggers a variety of stop signals that actively terminate the reaction. These active termination mechanisms include a switch in the type of arachidonic acid metabolite produced, from proinflammatory leukotrienes to anti-inflammatory lipoxins (described later), and the liberation of anti-inflammatory cytokines, including transforming growth factor-β (TGF-β) and IL-10, from macrophages and other cells. Other control mechanisms that have been demonstrated experimentally include neural impulses (cholinergic discharge), which inhibit the production of TNF in macrophages.
Leukocytes can eliminate microbes and dead cells by phagocytosis, followed by their destruction in phagolysosomes.
Destruction is caused by free radicals (ROS, NO) generated in activated leukocytes and by granule enzymes.
Neutrophils can extrude their nuclear contents to form extracellular nets that trap and destroy microbes.
Granule enzymes may be released into the extracellular environment.
The mechanisms that function to eliminate microbes and dead cells (the physiologic role of inflammation) also are capable of damaging normal tissues (the pathologic consequences of inflammation).
Anti-inflammatory mediators terminate the acute inflammatory reaction when it is no longer needed.
The mediators of inflammation are the substances that initiate and regulate inflammatory reactions. Although the harried student may find the list of mediators daunting (as do professors!), it is worthy of note that this knowledge has been used to design a large armamentarium of anti-inflammatory agents that are used every day by many people and which include familiar drugs such as aspirin and acetaminophen. The most important mediators of acute inflammation are vasoactive amines, lipid products (prostaglandins and leukotrienes), cytokines (including chemokines), and products of complement activation (
Table 3.5 ). We begin by summarizing the general properties of the
Table 3.5 Principal Mediators of Inflammation
Prostaglandins Mast cells, Vasodilation, pain, fever leukocytes http://ebooksmedicine.net mediators of inflammation and then discuss some of the more important molecules.