Acute Phase Response

The development of injury, infection, or cancer cachexia elicits an acute phase response. This is one of the most basic responses of the body to defend itself against injury. Phylogenetically, this response could be considered the most primitive response of the body. This stereotypical response is similar for injury from an accident, burn, infection, foreign objects, and, in some cases, from a tumor. Unfortunately, this response does not occur for most tumors, but it is seen when the malignancy presents with infection, such as in lung cancer, or in other more aggressive malignancy, such as seen in leukemia. The host develops a response that includes reductions in serum iron and zinc levels, increased serum copper and ceruloplasmin levels, alterations in amino acid distribution and metabolism, an increase in acute phase globulin synthesis, and glu-coneogenesis. Although not common, fever can occur, and a negative nitrogen balance results. The tumor can elicit a sequence of events that include changes in cytokine levels as well as several classical hormone levels. For example, a malignant process in the lung will attract monocytes that will be transformed into macrophages at the tissue site of tumor. These macrophages will secrete proteins known as cytokines and other peptides that can attract other white blood cells and initiate an inflammatory response common to many types of injury. Cyto-kines include TNF-a and IL-1 to IL-20. TNF and other cytokines circulate to the liver, inhibit albumin syntheses, and stimulate the synthesis of acute phase proteins. Acute phase proteins include C-reactive protein, which promotes phagocytosis, modulates the cellular immune response, and inhibits the migration of white blood cells into the tissues; a1-anti-chymotrypsin, which minimized tissue damage due to phagocytosis and reduces intravascular coagulation; and a2-macroglobulin, which forms complexes with proteases and removes then from circulation, maintains antibody production, and promotes granulo-poiesis and other acute phase proteins. Unfortunately, the majority of tumors do not elicit a large acute phase response. This limited response may result in a decreased inflammatory and tumor-cidal effect.

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