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An Urban Experience
cells (Langerhans cells), neurons, and keratinocytes.
One of the most important medical functions of corticosteroids is their anti-inflammatory
effect. GC stabilize the membranes of lysosomes so
that they rupture with difficulty. This helps prevent the usual tissue damage and destruction that occurs when lysosomal enzymes are released. GC also decrease the production of bradykinin, which is a potent vasodilating substance. That decreases the permeability of the capillary membrane, which then prevents protein leakage into inflamed tissues.
GC minimize the inflammatory response through the action of lipomodulin, which inhibits phospholipase
A2, the enzyme that normally converts membrane phospholipids into arachidonic acid (AA), a proinflammatory product. The decrease in AA limits available precursor molecules for lipoxygenase and cyclo-oxygenase to produce the AA-derived mediators of inflammation. Lastly, GC inhibit the expression of adhesion molecules on the endothelial cells (particularly ELAM-1 and ICAM-1) and thereby interfere with the movement of leukocytes from the vasculature into inflamed tissues. This is the cause of the commonly noted leukocytosis seen with GC administration.
GC block the inflammatory response to an allergic reaction exactly the same way that they block other types of inflammation. The basic allergic reaction between an antigen and antibody is not affected, and even some of the secondary effects of the allergic reaction, such as the release of histamine, still occur. However, the subsequent inflammatory response is responsible for many of the serious and sometimes fatal effects of the allergic reaction. Administration of GC can be lifesaving.
The specific GC effects that occur with their therapeutic use are summarized here and should be considered, particularly if ongoing therapy will be needed:
• Suppress the release of ACTH by the pituitary gland and,
therefore, suppress the release of corticosteroids by the
adrenal cortex.
• Reduce the number of circulating lymphocytes through
redistribution and suppress
• T lymphocyte function.
• Reduce the number of circulating eosinophils.
• Help maintain cell membrane activity.
• Inhibit macrophage function.
• Suppress antibody production.
• Inhibit the release of endogenous pyrogen (IL-1).
• Depress prostaglandin and leukotriene synthesis.
• Alter the complement and kinin cascades.
• Interfere with leukocyte migration and adhesion.
• Suppress lysosomal release from neutrophils by stabilizing
lysosomal membranes.
• Suppress phagocytosis.
• Reduce fibroblast activity resulting in delayed healing and
thinning of the skin.
• Affect enzyme actions and other cellular functions.
 Figure 3. Because of the complexity of the mediators produced by the immune system, treatment with antihistamines typically produces a poor response. Antihistamines aimed primarily at H1 and H2 recep- tors are a common treatment choice in veterinary medicine, but little evidence supports their efficacy in treating allergic skin disease.
Corticosteroids (examples: prednisolone, dexamethasone, methylprednisolone)
Historically, synthetic corticosteroids are a mainstay in effective treatment of allergic skin disease. Glucocorticoids (GC) are the primary corticosteroids used. As these natural hormones are produced by the adrenal gland and are essential for normal life, they diffuse into and affect the activity of every cell in the body. GC exert most of their actions by binding to intracytoplasmic steroid receptors, which are then transported to the nucleus where they bind to cellular DNA and alter gene expression (Figure 4)
 Figure 4. Synthetic corticosteroids, primarily glucocorticoids, are integral in effective treatment of allergic skin disease. GC exert most of their actions by binding to intracytoplasmic steroid receptors, which are then transported to the nucleus where they bind to cellular DNA and alter gene expression.
 42ND WORLD SMALL ANIMAL VETERINARY ASSOCIATION CONGRESS AND FECAVA 23RD EUROCONGRESS
  































































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