engleski

Acute Phase Proteins

Within the spectrum of systemic reaction to inflammation two physiological responses in particular are regarded as being associated with acute inflammation. The first involves the alteration of the temperature set-point in the hypotalamus and the generation of the febrile response. The second involves alterations in metabolism and gene regulation in the liver. Three cytokines that are released from the site of tissue injury -- IL-1, TNF- and IL-6 are considered to regulate the febrile response, possibly as a protective mechanism. At the same time, IL-1 and IL-6 can act on the adrenal pituitary axis to generate adrenocorticotropic hormone (ACTH) and, subsequently, induce the production of cortisol. This provides a negative feedback loop, since corticosteroids inhibit cytokine gene-expression. The second important aspect of the acute phase response is the radically altered biosynthetic profile of the liver. Under normal circumstances, the liver synthesizes a characteristic range of plasma proteins at steady state concentrations. Many of these proteins have important functions and higher plasma levels of these acute phase reactants (APRs) or acute phase proteins (APPs) are required during the acute phase response following an inflammatory stimulus. Although most APRs are synthesized by hepatocytes, some are produced by other cell types, including monocytes, endothelial cells, fibroblasts and adipocytes. Most APRs are induced between 50% and several-fold over normal levels. In contrast, the major APRs can increase to 1000-fold over normal levels. So-called negative APRs are decreased in plasma concentration during the acute phase response to allow an increase in the capacity of the liver to synthesize the induced APRs. APRs have a wide range of activities that contribute to host defence: they can directly neutralize inflammatory agents, help to minimize the extent of local tissue damage, as well as participate in tissue repair and regeneration. There is a rapid increase in the plasma concentration of many complement cascade components the activation of which ultimately results in the local accumulation of neutrophils, macrophages and plasma proteins. These participate in the killing of infectious agents, the clearance of foreign and host cellular debris, and the repair of damaged tissue. Coagulation components, such as fibrinogen, play an essential role in promoting wound healing. Proteinase inhibitors neutralize the lysosomal proteases released following the infiltration of activated neutrophils and macrophages, thus controlling the activity of the proinflammatory enzyme cascades. The increased plasma levels of some metal-binding proteins help prevent iron loss during infection and injury, also minimizing the level of haem iron avaible for uptake by bacteria and acting as scavenger for potentially damaging oxygen free radicals. Their interactions with other well-defined defence systems and the magnitute and rapidity of their induction following an acute phase stimulus, together with their short half-lifes, suggest a particularly critical requirement for these proteins very early in the establishment of host defence.

acute phase proteins

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