Inflammatory reactions underlie common chronic diseases, such as rheumatoid arthritis, atherosclerosis, and lung fibrosis, as well as life-threatening hypersensitivity reactions to insect bites, drugs, and toxins (Table 3.2 ). For this reason our pharmacies abound with anti-inflammatory drugs, which ideally would control the harmful sequelae of inflammation yet not interfere with its beneficial effects. In fact, inflammation may contribute to a variety of diseases that are thought to be primarily metabolic, degenerative, or genetic disorders, such as type 2 diabetes, Alzheimer disease, and cancer. Hence, anti-inflammatory drugs may well have a broader role than currently indicated. In recognition of the wide-ranging harmful consequences of inflammation, the lay press has rather melodramatically referred to it as “the silent killer.”
Not only excessive inflammation but also defective inflammation is responsible for serious illness. Too little inflammation, which is typically manifested by increased susceptibility to infections, is most often caused by a reduced number of leukocytes resulting from replacement of the bone marrow by cancers and suppression of the
Arthritis Lymphocytes, macrophages; antibodies?
Listed are selected examples of diseases in which the inflammatory response plays a significant role in tissue injury. Some, such as asthma, can present with acute inflammation or a chronic illness with repeated bouts of acute exacerbation.These diseases and their pathogenesis are discussed in relevant chapters.
marrow by therapies for cancer and graft rejection. Recall that leukocytes, the cells of the inflammatory response, arise from progenitors in the bone marrow, hence any compromise of marrow function will diminish the generation of mature leukocytes. Inherited genetic abnormalities of leukocyte function are rare disorders but they provide valuable information about the mechanisms of leukocyte responses. These conditions are described in Chapter 5, in the context of immunodeficiency diseases.
Inflammation is terminated when the offending agent is eliminated. The reaction resolves because mediators are broken down and dissipated, and leukocytes have short life spans in tissues. In addition, anti-inflammatory mechanisms are activated, serving to control the response and prevent it from causing excessive damage to the host. After inflammation has achieved its goal of eliminating the offending agents, it sets into motion the process of tissue repair. Repair consists of a series of events that heal damaged tissue. In this process, the injured tissue is replaced through regeneration of surviving cells and filling of residual defects with connective tissue (scarring).
This chapter describes the etiology of and stimuli for inflammation, and then the sequence of events, mediators, and morphologic patterns of acute inflammation. This is followed by a discussion of chronic inflammation, and then the process of tissue repair.
Inflammatory reactions may be triggered by a variety of stimuli: • Infections (bacterial, viral, fungal, parasitic) and microbial toxins are among the most common and medically important causes of inflammation. Different infectious pathogens elicit distinct inflammatory responses, from mild acute inflammation that causes little or no lasting damage and successfully eradicates the infection, to severe systemic reactions that can be fatal, to prolonged chronic reactions that cause extensive tissue injury. The morphologic pattern of the response can be useful in identifying its etiology, as discussed later in this chapter.
Tissue necrosis elicits inflammation regardless of the cause of cell death, which may include ischemia (reduced blood flow, the cause of myocardial infarction), trauma, and physical and chemical injury (e.g., thermal injury, as in burns or frostbite; irradiation; exposure to some environmental chemicals). Several molecules released from necrotic cells are known to trigger inflammation; some of these are described later.