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Arachidonic acid – The substance that is a pre- cursor of inflammatory mediators such as prostaglandins and leukotrienes
Chemokines – An agent of the inflammatory process that attracts or recruits cells to the site
Cyclooxygenase pathway – One arm of the arachidonic acid cascade that leads to pro- duction of prostaglandins and thromboxanes
Cytokines – Proteins produced by a cell to modulate the actions of other cells; also known as messenger proteins
Growth factors – The molecules that stimulate cell growth or activation
Lipoxygenase pathway – One arm of the arachidonic acid cascade that leads to pro- duction of leukotrienes and lipoxins
Matrix metalloproteinases (MMP) – Agents of the inflammatory process that degrade the extracellular matrix
Phagocytosis – The process by which white blood cells ingest debris or micro- organisms
To regulate the inflammatory response, numerous endogenous agents have been em- ployed. IL-4 and IL-10 inhibit cytokine production. PGE2 can either stimulate or inhibit inflammation indirectly. Several other agents are competitive inhibitors of inflammation. Read more
Inflammatory mediators often play important roles in the normal cell, regulating the synthesis and turnover of ECM, for ex- ample. Accordingly, blocking their production can have adverse effects on normal cell physiology. At best, inflammation can be controlled by modulating the production of these mediators.
Inflammation may be initiated by either en- dogenous or exogenous factors. It can be an acute response to trauma (as in a ligament tear) or a chronic response (as in autoim- mune diseases such as RA). Infection and crystalline deposits also can provoke an in- flammatory response that will persist until the underlying cause is eliminated.
The immune response to an antigen can be classified as humoral (antibody based) or cell mediated. Both processes require lympho- cytes and antigen-presenting cells (APCs), which may be lymphocytes, macrophages, or dendritic cells. Lymphocytes are de- scribed as B cells or T cells, a naming con- vention based on the site of their original differentiation—bone marrow (B cells) or thymus (T cells).5
Humoral immunity occurs through B cells, which produce soluble, membrane- bound immunoglobulin (antibody) for a spe- cific antigen. Cell-mediated immunity occurs through T cells that recognize an antigen when it is bound to a major histocompatibility complex (MHC) molecule, also termed a human leukocyte antigen (HLA). Thus, B cells are frequently the APCs to the T-cell receptors. Binding of the APCs with the T-cell receptors stimulates division of T cells into one of two types of helper cells (Th1 or Th2) and secretion of numerous cytokines that in- duce an inflammatory response (Fig. 3).
There are two classes of MHC molecules (class I and II), both of which contain a large number of alleles (variable regions). Although MHC molecules bind antigens, they differ from B-cell receptors in that MHC molecules are expressed by a number of cell types. They also lack the specificity of the antibodies produced by B cells. Several chronic inflammatory diseases, such as RA, are associated with distinct alleles that may confer genetic predisposition to the disease. That the inflammation persists or recurs in these chronic diseases indicates that at- tempts to achieve homeostasis are impeded, possibly by a recurrent trigger.
In response to a trigger, such as an injury or an antigen, cells in affected tissue produce signals to initiate the infiltration of white blood cells (such as monocytes, granulocytes, and lymphocytes) to the site.
Inflammation is characterized by erythema, warmth, pain, and edema. Acute in-flammation generally occurs in response to an injury or introduction of foreign mate- rial at a specific site and is an important part of wound healing. Read more
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