Inflammatory sites

Tissue distribution of lipo-preparations. The tissue distribution of lipid microspheres in normal and pathologic animals was studied. Research into liposomes of similar size suggested that lipid microspheres accumulated preferentially in the reticuloendothelial system, inflammatory sites, or certain tumors. The distribution of lipid microspheres to these tissues has been found in our studies (7,2). Interestingly, our study showed that lipid microspheres accumulated, particularly at high concentrations, in damaged vascular walls such as atherosclerotic vascular walls. 

In view of the fact that neutrophils isolated from some inflammatory sites have been exposed to agents that selectively activate their gene expression (which may result in the expression of FcyRI see Fig. 7.9 and 8.9), such molecular adaptation of neutrophils to their environment may indeed occur. 

It has been appreciated for many years that monocytes and macrophages are important producers of IL-1 at inflammatory sites. Thus, it is now recognised that neutrophils can also secrete this cytokine following appropriate stimulation, but there are two important differences in the mechanisms that regulate IL-1 production in these cell types ... 

Which chemokines attract Tregs to inflammatory sites and which cytokines stimulate their proliferation during inflammation ... 

Macrophage release of chemotactic factors also attracts fibroblasts, an effect that has been studied in animals and humans. The factors are sufficiently strong and specific that fibroblasts migrate up a concentration gradient (tested in artificial chambers) and can induce replication (in vivo experiments). Thus, fibroblasts—the primary source of structural proteins, notably collagen— can be mobilized by AM to the inflammatory sites and can also markedly increase in number in response to secretion of activated AMs. These factors, in addition to the other activities and secretions of the AM, are being characterized (Gee, 1984). 

Metabolites of arachidonic acid, including prostaglandins (PG), thromboxanes, and leukotrienes, are considered strong candidates as mediators of the inflammatory process. Steroids may exert a primary effect at the inflammatory site by inducing the synthesis of a group of proteins called lipocortins. These proteins suppress the activation of phospholipase A2, thereby decreasing the release of arachidonic acid and the production of proinflammatory eicosanoids (Fig. 60.6). 

Reduced capillary permeability and edema at the inflammatory site Increased prostaglandin formation Enhanced formation of interleukins (lL-1, lL-2)... 

It acts peripherally by inhibiting the synthesis of prostaglandins by reversible inhibition of cyclooxygenase. Inhibition of the migration of leukocytes to an inflammatory site and inhibition of the release of lysosomal enzymes may also be involved in the antiinflammatory action. 

Extracellular S100A8/A9 heterodimer exhibits cytokine-like functions, e.g. enhancing leukocyte recruitment to inflammatory sites and AA transportation to target cells (Vandal et al., 2003 Kerkhoff et al., 1999 Eue and Sorg, 2001). 

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. 

Its mechanism of action, however, is not completely elucidated. Kamakura et aL [94] studied the effects of stem bromelain on tlw plasma kallikrein system, bradykinin levels and plasma exudation at the inflammatory site in rats with a kaolin-induced inflammation of an air couch. Bromelain caused a dose-... 

Relief of inflammatory symptoms Glucocorticoids dramatically reduce the manifestations of inflammations (for example, rheumatoid and osteoarthritic inflammations, inflammatory conditions of the skin), including the redness, swelling, heat, and tenderness that are commonly present at the inflammatory site. The effect of glucocorticoids on the inflammatory process is the result of their effects on the distribution, concentration, and function of leuko-... 

Prostaglandins such as PGEj are potent vasodilators, so they increase blood flow. Local vasodilation occurs at inflammatory sites. Aspirin irreversibly inhibits cyclooxygenase. A single serine residue in the enzyme is acetylated as follows ... 

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