An acute hypermetabolic and inflammatory response is often observed following major illness or trauma, such as a severe burn. Increases in acute-phase protein, proinflammatory cytokine, and catabolic hormone levels raise energy requirements, resulting in muscle wasting, nitrogen imbalance, and futile substrate cycling of glucose and triglycerides. When this acute posttraumatic response is aggravated and prolonged, it results in multiple organ dysfunction syndrome and, eventually, death. The common denominators of the acute-phase response are the activation of the immune system, with overproduction of proinflammatory cytokines and depression of anti-inflammatory cytokines, and associated changes in neurological, metabolic, and endocrine functions irrespective of the diverse underlying pathologic conditions.11,15 Most endocrine cells are directly affected by all cytokines that are released during the acute-phase response, and profound changes in the hormonal balance accompany this response.16 This acute inflammatory response is associated with increased tissue needs for nutrients that are required for augmented demands related to increased substrate oxidation because of fever and to tissue remodeling and repair. Circulating cytokines contribute to this beneficial response by stimulating hormones and cellular processes that increase substrate uptake, mobilization, cellular transport, and metabolism. In contrast, prolonged elevation of cytokine levels may contribute to the development of insulin resistance and other catabolic responses mediated by abnormal release of hormones.17 There is evidence that cytokines induce strong inhibitory hypothalamic signals for GH secretion. Interleukin 1β stimulates release of somatostatin, which in turn inhibits release of GH.18 This stimulating effect on somatostatin is shared with TNF-α and IL-6, with a synergism between TNF-α and IL-1β.19,20 At the level of the pituitary gland, IL-6 has been reported to have a positive effect, which may explain the elevated levels of GH in patients with inflammatory diseases or experimental endotoxemia.21 However, in clinical experience, growth retardation usually follows prolonged periods of infection and inflammation, suggesting that the acute-phase response may cause resistance to GH and IGF-1.22 Together with the former systemic response, the long-term paracrine effects of synergistically acting proinflammatory cytokines secreted in high local concentrations in tissues infiltrated by inflammatory cells may alter or inhibit the normal function of mesenchymal and endothelial cells and, in some cases, even cause cell destruction.