Application of Acute Phase Proteins for Monitoring Inflammatory States in Cattle

Abstract

The animal body functions in a controlled internal environment, strictly regulated by a variety of homeostatic mechanisms. However, the internal milieu is disturbed by external factors that lead to imbalance of the inner homeostasis. The host is equipped with multiple tools to abolish external challenges like tissue injury and infection by activation of various defense mechanisms; however, mobilization of all these responses is associated with alterations of the homeostatic status. The multifaceted immune and metabolic responses of the host to external challenges are commonly referred to as the acute-phase response (APR) (Kushner, 1982; Koj, 1985; Baumann & Gauldie, 1994; Moshage, 1997; Mackiewicz, 1997). The aim of the APR is to eliminate the agent(s) that caused the interference and to bring the homeostasis back to normality (Figure 1). The APR is initiated in response to a variety of stimuli including acute trauma, bacterial infection, surgery, fracture, burns, tissue necrosis, presence of a chronic disease, or ongoing inflammatory processes (Kushner, 1982; Gordon & Koj, 1985; Baumann & Gauldie, 1994; Steel & Whitehead, 1994; Boosalis et al., 1996; Mackiewicz, 1997). The APR usually resolves within a few days or weeks, however sometimes it can persist when the causal agent is defiant (Boosalis et al., 1996; Mackiewicz, 1997; Koj, 1998). The APR is regulated by numerous compounds referred to as cytokines (Mackiewicz, 1997; Koj, 1998; Martin et al., 1999). The latter are produced by macrophages, when they are activated by bacterial endotoxin, viruses, free radicals, prostaglandins, or other factors released under different inflammatory conditions. The main cytokines released by macrophages are interleukin-1 (IL-1), IL-8, tumor necrosis factor-alpha (TNF-), and interferon-gamma (INF-) (Koj, 1998; Martin et al., 1999). The release of proinflammatory cytokines, at the site of tissue injury, stimulates various other cell types to produce a cascade of other cytokines, including IL-6-type cytokines, which act to stimulate the production of acute phase proteins (APP) from liver hepatocytes or other tissues (Baigrie et al., 1991; Mackiewicz, 1997). Although the production of cytokines in the liver or other local sites is complex, it is believed that IL-1 and IL-6 are the two main stimulants of APP production (Gauldie et al., 1987; Nijsten et al., 1991; Ohzato et al., 1992).