A complex cascade of events, known as the acute phase response, is immediately initiated by the body on infection or injury. There are local and systemic components to this response, both of which cause physiological changes that range from coagulation and cell migration to fever and increased hormone secretion. In this article Andrew Stadnyk andlack Gauldie examine the acute phase response to parasitism and discuss its influence on the outcome of infection.
The acute phase response in inflammation
Acute inflammation is the organism's normal homeostatic immediate physiological response to injury or infection. Its primary role is to maintain the integrity of the tissue by restricting damage to the injured site. The acute phase response (APR) in inflammation may be divided into two phases: the local response, involving coagulation, kinin generation, phospholipid metabolism with vasodilation and cellular emigration, and the systemic response, including fever, leukocytosis, changes in the concentrations of plasma heavy metals, and increased plasma levels of a number of hepatocyte-derived proteins along with modifications to amino acid pools'-'. Endocrine changes include increases in cortisol, glucagon, catecholamines and thyroid hormones. The net sum of these acute changes, summarized in Fig. 1, is a general enhancement of body metabolism including increased protein catabolism, increased gluconeogenesis and a negative nitrogen balance.
The response is triggered by blood-borne mediators released from activated local tissues and includes products of phospholipid metabolism and polypeptide hormone-like mediators, or cytokines, which have a broad range of physiological effects. Tissue macrophages and peripheral blood monocytes are the cells most likely to initiate the process, as they become activated upon encounter with a foreign organism such as a parasite. These cells are potent sources of early-acting 'alarm' cytokines including interleukin 1 (IL-l) and tumor necrosis factor (TNF). These early cytokines act on adjacent tissue cells, including fibroblasts and endothelial cells, causing activation, modulation of cell surface components and release of further cytokines in a cascade responses-'.
At the local level, vascular permeability changes occur immediately, particularly at the post-capillary venules, due to the action of prostaglandins, leukotrienes and other vasoactive and kinin-like mediators. This results in tissue edema and may be associated with pain. These developments are accompanied by vascular events such as platelet aggregation (a reaction mediated by thrombin, adenosine compounds or platelet-activating factor (PAF)) that results in release of peptides such as transforming growth factor B (TGF-B), platelet factor 4 (PF4) and B-thromboglobulin (BTG). These mediators, along