Inflammation Capillary permeability

The classical skin response to local release of histamine that results from contact with an allergen, irritant or following an insect bite. A central wheal develops as a direct result of local inflammation and the the oedema the follows the increased capillary permeability caused by histamine acting on HI-receptors on vascular-endothelial cells. 

In addition to the reports of uptake of intact small liposomes (SUV) by hepatocytes (Scherphof et al., 1983), there is some evidence of uptake of intravenously administered liposomes as intact structures by cells other than mononuclear phagocytes of the MPS. Recently, the integrity of the capillary endothelial barrier in several pathophysiological conditions was discussed (Bodor and Brewster, 1986). Several studies already indicated an increased capillary permeability during inflammation both in animals (Lopez-Berestein et al., 1984a) and in man (Morgan et al., 1985 Williams et al., 1987). 

As observed by Celus, a Roman physician during the first century A.D., the four cardinal signs characterize inflammation swelling, redness, heat, and pain. Swelling/edema occurs in response to the accumulation of fluids from damaged capillaries following injury. Increased fluid accumulation leads to increase capillary permeability. Histamine, produced and released by resident mast cells, also... 

Increased capillary permeability may allow plasma proteins to leak into the interstitial spaces of a tissue. The presence of excess protein in these spaces causes an increase in interstitial fluid colloid osmotic pressure and pulls more fluid out of the capillaries. Mediators of inflammation such as histamine and bradykinin, which are active following tissue injury and during allergic reactions, increase capillary permeability and cause swelling. 

Histamine, which promotes bronchoconstriction as well as the vasodilation and increased capillary permeability that lead to inflammation... 

Glucocorticosteroids are the most potent antiinflammatory agents available. They stabilize lysosomal membranes and reduce the concentration of proteolytic enzymes at the site of inflammation. They promote the synthesis of proteins called lipocortins which inhibit phospholipase-A2 and thus inhibit production of arachidonic acid, leukotrienes and prostaglandins. Furthermore, the expression of COX-II and through that the inflammatory effects of the licosanoids is inhibited. Glucocorticosteroids reduce the release of histamine from basophils, decrease capillary permeability and cause vasoconstriction. Glucocorticosteroids stimulate the loss of calcium with the urine and inhibit the resorption of calcium from the gut. 

Mechanism of Action An adrenocortical steroid that controls the rate of protein synthesis, depresses the migration of polymorphonuclear leukocytes and fibroblasts, reduces capillary permeability, and prevents or controls inflammation. Therapeutic Effect Decreases tissue response to inflammatory process. 

Mecfianism of Action A high-potency, fluorinated corticosteroid that decreases inflammation by suppression of migration of polymorphonuclar leukocytes and reversal of increased capillary permeability. The exact mechanism of the anti-inflammatory process is unclear. T fierapeuticEffect Decreases or prevents tissue response to the inflammatory process. 

Mechanism of Action An adrenocortical steroid that suppresses migration of polymorphonuclear leukocytes and reverses increased capillary permeability Therapeutic Effect Decreases inflammation. 

Antiinflammatory and immunosuppressive effects Glucocorticoids suppress all types of inflammation, hypersensitization and allergic reactions. They suppress the edema, capillary dilatation, migration of leukocytes, capillary permeability in the inflamed area. 

Muscle cells release kallikrein during inflammation causing formation of active kinin peptides (bradykinin and kallidin) from kininogen [65, 66]. Kinins are peptide hormones that produce vasodilation, increase capillary permeability, and cause pain and infiltration of neutrophils. There is a direct correlation between the amount of kinin in plasma or tissues and the degree of inflammation. Vascular dilation causes increased blood flow to infection [67, 68], Bik inhibits formation of kinins and vascular dilation by kallikrein, thereby inhibiting smooth muscle contraction [69-71],... 

Bradykinin and related kinin peptides are produced by leucocytes and act via Gaq to elevate cytosolic Ca2+ and promote nitric oxide (NO) synthesis, smooth muscle contraction, capillary permeability, inflammation and histamine release from mast cells. 

Evidence indicates that steroids affect other cells and substances that modulate inflammation. Exposure of human basophils to steroid in culture inhibits histamine release induced by an IgE-dependent stimulus. Steroids inhibit phospholipase A2, which prevents biosynthesis of arachidonic acid and subsequent formation of prostacyclin, thromboxane A, prostaglandins, and leukotrienes. Steroids also decrease capillary permeability and fibroblast proliferation and the quantity of collagen deposition, thereby influencing tissue regeneration and repair. 

The classical inflammation criteria such as exudation, cellulation and proliferation can only be applied to the liver with some reservations, since the emphasis in this instance is on the sinusoids, which already display maximum permeability under normal conditions. The increase in capillary permeability, required by the definition of infiammation, is really only applicable to the area of the vascularized portal fields, e.g. in purulent cholangitis. The definition of inflammation can only be applied to classic acute viral hepatitis, (s. p. 415)... 

A healthy immune system is able to destroy most antigens. During that time the patient experiences signs of inflammation (see 12.2 Signs of Inflammation). The inflammatory response is brought about by prostaglandins that cause vasodilatation, relax smooth muscles, and make capillaries permeable and sensitize nerve cells within... 

Effects on inflammation and pain E- and F-series PGs are known to be released in the inflammation and increase capillary permeability, producing edema and painful erythema. PGE, can produce this in quantities as low as 1 (ig PGFla requires about 1 jig. Erythema produced by an intradermal application may persist for 10 h. There is evidence that PGs Ej, E2, A2, and F2ot stimulate (potentiate ) histamine and bradykinin. Low concentrations of PGs induce hyperalgesia. This appears to be a sensitization of pain receptors. It was also demonstrated that subdermal infusion of PGE only pro-... 

As mentioned previously (page 64), Spector and Willoughby have suggested that some of the vascular phenomena occurring in tissue injury may be the result of the local destruction of adrenaline-like vasoconstrictor compounds. They measured increased capillary permeability in rats subjected to thermal injury and turpentine-induced pleurisy. The subcutaneous administration of five monoamine oxidase inhibitors, including iproniazid, markedly inhibits both types of inflammation. Iproniazid inhibition can be completely antagonized by the intravenous injection of the adrenolytic substance, dibenamine, but not by adrenalectomy. A subcutaneous dose of... 

Mention should be made at this juncture of the role of adrenolytic drugs as inhibitors of inflammation. Spector and Willoughby found that diben-amine hydrochloride antagonizes the anti-inflammatory effect of iproniazid, but other workers have shown that adrenolytic drugs themselves reduce capillary permeability , and that dibenamine hydrochloride suppresses the tuberculin reaction in the guinea-pig . 

The concept of a proteolytic mechanism in the production of inflammatory manifestations is supported by the demonstration of anti-inflammatory activity in various protease inhibitors, e.g. the trypsin inhibitors of the pancreas, soya bean, ovomucoid and potato . It is interesting to note that the inhibitor from potatoes exerts its effect even after the inflammation is well established , suggesting that protease action is a continuing feature of inflammation and not simply an initiating process. Various esterase inhibitors (dyflos, quinine, quinidine and chloroquine) also reduce capillary permeability induced by heat and the permeability globulins . 

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