ABSTRACT
Pleiotropic Effects of Regular Exercise .................................................................... 298 21.5 Conclusions and Future Directions .......................................................................................299 Take-Home Messages ....................................................................................................................299 References ......................................................................................................................................300
mechanical stresses. Regardless of the inciting factors, the events accompanying inammation are somewhat consistent. The local response to infections or tissue injury involves the production of cytokines that are released at the site of inammation. Cytokines are small polypeptides, which were originally discovered to have immunoregulatory roles (Majno and Joris 2004). Some of these cytokines facilitate the inux of lymphocytes, neutrophils, monocytes, and other cells. The local inammatory response is accompanied by a systemic response known as the acute-phase response (Table 21.1). This response includes the production of a large number of hepatocyte-derived acute phase proteins, such as C-reactive protein (CRP), and can be mimicked by the injection of the cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, or IL-6 into laboratory animals or humans (Majno and Joris 2004; Pedersen 2006; Edwards et al. 2007). The initial cytokines in the cytokine cascade are TNF-α, IL-1, IL-6, IL-1 receptor antagonist (IL-1ra), and soluble TNF-α receptors (sTNF-R). IL-1ra inhibits IL-1 signal transduction and sTNF-R represents the naturally occurring inhibitors of TNF-α (Majno and Joris 2004; Luster et al. 2005). In response to an acute infection or trauma, the cytokines and inhibitors may increase several-fold and decrease when the infection or trauma is healed. Additionally, these acute phase reactants have considerable effects on the metabolism during acute illness, leading to hyperglycemia, insulin resistance, and increased glucogenesis (Jenkins and Ross 1999). Elevation in these markers also increases proteolysis (Hasselgren 1999), bone resorption (Smith et al. 2002), and dyslipidemia (Marik 2006), in addition to upregulating other members of the inammatory cascade, each of which has its own downstream biologic effects (Table 21.1).
