Cytokines cHAPTER 12 277 (b) Cytokine-producing cell Autocrine action Paracrine action Nearby cell Gene Target cell Endocrine action Distant cell Biological effects JRE 12-1(a)Overview of the induction and function of es. (b)Most cytokines exhibit autocrine and/or paracrine action fewer exhibit endocrine action effects of the individual cytokines. In some cases, cytokines of cytokines, the chemokines, a group of low-molecular- exhibit antagonism; that is, the effects of one cytokine inhibit weight cytokines that affect chemotaxis and other aspects or offset the effects of another cytokine Cascade induction of leukocyte behavior. These molecules play an important occurs when the action of one cytokine on a target cell role in the inflammatory response and are described in induces that cell to produce one or more other cytokines, Chapter 15 which in turn may induce other target cells to produce other Because cytokines share many properties with hormones cytokines and growth factors, the distinction between these three The term cytokine encompasses those cytokines secreted classes of mediators is often blurred. All three are secreted by lymphocytes, substances formerly known as lympho- soluble factors that elicit their biological effects at picomolar kines, and those secreted by monocytes and macrophages, concentrations by binding to receptors on target cells substances formerly known as monokines. Although these growth factors tend to be produced constitutively, whereas other two terms continue to be used, they are misleading tokines and hormones are secreted in response to discrete because secretion of many lymphokines and monokines is stimuli, and secretion is short-lived, generally ranging from a not limited to lymphocytes and monocytes as these terms few hours to a few days. Unlike hormones, which generally imply, but extends to a broad spectrum of cells and types. act long range in an endocrine fashion, most cytokines act For this reason, the more inclusive term cytokine is preferred. over a short distance in an autocrine or paracrine fashion. In lany cytokines are referred to as interleukins, a name addition, most hormones are produced by specialized glands indicating that they are secreted by some leukocytes and act and tend to have a unique action on one or a few types of tar upon other leukocytes. Interleukins 1-25 have been identi- get cell. In contrast, cytokines are often produced by, and fied. There is that still other cytokines will bind to, a variety of cells be discovered and that the interleukin group will expand The activity of cytokines was first recognized in the mid further. Some cytokines are known by common names, 1960s, when supernatants derived from in vitro cultures of including the interferons and tumor necrosis factors. Re- lymphocytes were found to contain factors that could regulate cently gaining prominence is yet another another subgroup proliferation, differentiation, and maturation of allogeneiceffects of the individual cytokines. In some cases, cytokines exhibit antagonism; that is, the effects of one cytokine inhibit or offset the effects of another cytokine. Cascade induction occurs when the action of one cytokine on a target cell induces that cell to produce one or more other cytokines, which in turn may induce other target cells to produce other cytokines. The term cytokine encompasses those cytokines secreted by lymphocytes, substances formerly known as lympho￾kines, and those secreted by monocytes and macrophages, substances formerly known as monokines. Although these other two terms continue to be used, they are misleading because secretion of many lymphokines and monokines is not limited to lymphocytes and monocytes as these terms imply, but extends to a broad spectrum of cells and types. For this reason, the more inclusive term cytokine is preferred. Many cytokines are referred to as interleukins, a name indicating that they are secreted by some leukocytes and act upon other leukocytes. Interleukins 1–25 have been identi￾fied. There is reason to suppose that still other cytokines will be discovered and that the interleukin group will expand further. Some cytokines are known by common names, including the interferons and tumor necrosis factors. Re￾cently gaining prominence is yet another another subgroup of cytokines, the chemokines, a group of low-molecular￾weight cytokines that affect chemotaxis and other aspects of leukocyte behavior. These molecules play an important role in the inflammatory response and are described in Chapter 15. Because cytokines share many properties with hormones and growth factors, the distinction between these three classes of mediators is often blurred. All three are secreted soluble factors that elicit their biological effects at picomolar concentrations by binding to receptors on target cells. Growth factors tend to be produced constitutively, whereas cytokines and hormones are secreted in response to discrete stimuli, and secretion is short-lived, generally ranging from a few hours to a few days. Unlike hormones, which generally act long range in an endocrine fashion, most cytokines act over a short distance in an autocrine or paracrine fashion. In addition, most hormones are produced by specialized glands and tend to have a unique action on one or a few types of tar￾get cell. In contrast, cytokines are often produced by, and bind to, a variety of cells. The activity of cytokines was first recognized in the mid- 1960s, when supernatants derived from in vitro cultures of lymphocytes were found to contain factors that could regulate proliferation, differentiation, and maturation of allogeneic Cytokines CHAPTER 12 277 Gene activation Biological effects Signal Cytokine gene Inducing stimulus (a) Cytokine-producing cell Target cell Cytokine Receptor (b) Endocrine action Circulation Distant cell Paracrine action Nearby cell Autocrine action FIGURE 12-1 (a) Overview of the induction and function of cytokines. (b) Most cytokines exhibit autocrine and/or paracrine action; fewer exhibit endocrine action