When Lewis discovered the role of histamine in inflammation, one mediator was thought to be enough. Now, we are wallowing in them! Yet, from this large compendium, it is likely that a few mediators are most important for the reactions of acute inflammation in vivo, and these are summarized in
Table 3.8 . This list is compiled in part from the
Table 3.8 Role of Mediators in Different Reactions of Inflammation
Reaction of Inflammation Principal Mediators
Increased vascular Histamine permeability C3a and C5a (by liberating vasoactive amines from mast cells, other cells) Leukotrienes C4, D4, E4
Chemotaxis, leukocyte TNF, IL-1 recruitment and Chemokines activation C3a, C5a
Fever IL-1,TNF Prostaglandins
Tissue damage Lysosomal enzymes of leukocytes Reactive oxygen species http://ebooksmedicine.net observed anti-inflammatory effects of antagonists to these molecules, thus highlighting the importance of basic biology to the practice of medicine. The redundancy of the mediators and their actions ensures that this protective response remains robust and is not readily subverted.
Vasoactive amines, mainly histamine: vasodilation and increased vascular permeability
Arachidonic acid metabolites (prostaglandins and leukotrienes):several forms exist and are involved in vascular reactions, leukocyte chemotaxis, and other reactions of inflammation; antagonized by lipoxins
Cytokines: proteins produced by many cell types; usually act at short range; mediate multiple effects, mainly in leukocyte recruitment and migration; principal ones in acute inflammation are TNF, IL-1, and chemokines
Complement proteins: Activation of the complement system by microbes or antibodies leads to the generation of multiple breakdown products, which are responsible for leukocyte chemotaxis, opsonization and phagocytosis of microbes and other particles, and cell killing
Kinins:produced by proteolytic cleavage of precursors;mediate vascular reaction, pain
The morphologic hallmarks of acute inflammatory reactions are dilation of small blood vessels and accumulation of leukocytes and fluid in the extravascular tissue.
The vascular and cellular reactions account for the signs and symptoms of the inflammatory response. Increased blood flow to the injured area and increased vascular permeability lead to the accumulation of extravascular fluid rich in plasma proteins (edema) and account for the redness (rubor), warmth (calor), and swelling (tumor) that accompany acute inflammation. Leukocytes that are recruited and activated by the offending agent and by endogenous mediators may release toxic metabolites and proteases extracellularly, causing tissue damage and loss of function (functio laesa). During the damage, and in part as a result of the liberation of prostaglandins, neuropeptides, and cytokines, one of the local symptoms is pain (dolor).
Although these general features are characteristic of most acute inflammatory reactions, special morphologic patterns are often superimposed on them, depending on the severity of the reaction, its specific cause, and the particular tissue and site involved. The importance of recognizing distinct gross and microscopic patterns of inflammation is that they often provide valuable clues about the underlying cause.
Serous inflammation is marked by the exudation of cell-poor fluid into spaces created by injury to surface epithelia
Fig. 3.12 Serous inflammation. Low-power view of a cross section of a skin blister showing the epidermis separated from the dermis by a focal collection of serous effusion.