Inflammatory response early phase

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

Cromolyn and nedocromil are inhaled anti-inflammatory agents that block both the early- and late-phase response. Both agents are considered alternative therapies to inhaled corticosteroids for the treatment of mild persistent asthma however, both are less effective than low doses of inhaled corticosteroids.2,30 The exact mechanism of action of these agents is not understood, but they appear to inhibit mast cell mediator release as well as modulate other inflammatory responses.3... 

When injected, azathioprine (Imuran) is rapidly converted to 6-mercaptopurine. The half-life of azathioprine after intravenous injection is 10 to 20 min, and that of 6-mercaptopurine is somewhat longer. The cytotoxic activity of these thiopurines is due to the conversion of mercaptopurine to 6-thiouric acid, a noncarcinostatic metabolite. This action is thought to block the excess synthesis of inosinic acid from its precursors, glutamine and phosphoribosylpyrophosphate. In addition, unlike cyclophosphamide, azathioprine is a potent anti-inflammatory substance that can cause a reduction in the number of monocytes and neutrophils at inflammatory sites. Antibody responses are also inhibited by azathioprine. Studies in humans have shown that azathioprine decreases the y-globulin and antibody levels, thus influencing IgG rather than IgM production. This makes azathioprine an effective immunosuppressant in the early phases of immune responses. It is less effective or completely ineffective in altering either the effector phase or already established reactivities. 

Shock-dependent initialising mechanisms cause the induction of iNOS, COX-2, and CD 14. The early response genes, iNOS and COX-2, promote the inflammatory response by the rapid and excessive production of NO and prostaglandins. The transcription factor hypoxia-inducible factor-1 (HIF-1) may also regulate the induction of iNOS during the ischemic phase of shock, contributing to the excess NO formation. 

Inhibits early-phase allergic reaction and migration of inflammatory cells into nasal tissue and decreases response to seasonal and perennial rhinitis. 

Corticosteroids suppress all phases of the inflammatory response, including the early swelling, redness and pain and the later stages seen in chronic inflammation. Circulating lymphocytes and macrophages are reduced in number and the formation of prostaglandins and leukotrienes is inhibited via inhibition of phospholipase A2. Phospholipase A2 is the enzyme that converts cell membrane phospholipids into arachidonic acid. (See Figure 7.1.)... 

---