Energy regulation in inflammation-induced anorexia: implications for treatment.

sources of energy and substrate for repair. The outcome of local and systemic inflammation is an integrated metabolic response aimed at fighting infection, promoting wound healing, and restoring homeostasis. Although beneficial, the inflammatory response can lead to malnutrition and significant loss of body tissue, if severe or prolonged. Because body protein has no inactive storage form, the loss of protein translates into loss of functional tissue. Functional deficits can occur fewer than 7 d after the onset of acute inflammation. 3 Consequences of these deficits are compromised immunity, decreased wound healing, and suboptimal responses to therapeutic treatments.3 Thus, it is important to intervene early after the onset of acute inflammation to limit tissue loss and minimize the risk of complications. The provision of supplemental nutrition support is the most common intervention used to limit the negative nutritional consequences associated with systemic inflammation. Initially, nutrition support was based on the belief that providing sufficient calories to meet increased energy needs would decrease protein catabolism by lessening the demand for protein as a source of substrate for glucose.4 It was subsequently shown that the increased demand for substrates was not the primary mechanism driving the metabolic response to inflammation. 5 It is now known that, regardless of the level of increased energy required for recovery, there are limits to the amount of calories that can be safely provided. Glucose infusions that exceed the oxidative capacity of the body (; 5m gz kg 21 z min 21 ) result in lipogenesis, increased CO2 production, and fatty deposits in the liver, with no further improvement in nitrogen balance. Current nutrition-based interventions are focused more broadly on providing metabolic support, which includes customized macronutrients, micronutrients, and vitamins that are compatible with the patient’s metabolic state. 6 These interventions have been developed primarily for nutrients provided by enteral and parenteral routes. In light of the consensus that oral nutrition intake is preferred when not contraindicated, greater attention to development of interventions that reverse inflammation-induced anorexia and promote oral intake is warranted. Proinflammatory cytokines released during inflammation play a major role in mediating many of the symptoms associated with the systemic inflammatory response. 7 This recognition has led to growing interest among researchers and clinicians in the potential of blocking proinflammatory cytokine activity as an intervention to reverse inflammation-induced anorexia and weight loss. Several potential strategies are currently under study: 1) blocking cytokine-receptor binding through the administration of receptor antagonists, soluble receptors, and neutralizing antibodies; 2) inhibiting cytokine protein synthesis by suppressing enzymes responsible for conversion of cytokine precursors into active proteins; 3) blocking cytokine signal transduction or transcription factors; and 4) decreasing levels of cytokine intermediates such as arachidonic-acid metabolites.7,8 To date, none of these strategies has targeted site-specific inhibition of proinflammatory cytokine activity, such as feeding-related centers in the hypothalamus. Although cell- or tissue-specific inhibition of cytokine activity likely will be developed, administration of non-specific inhibitors should be done with caution in the interim. The inflammatory response is essential for recovery from cellular injury and infection. Therefore, non-specific blocking of proinflammatory cytokine activity may have significant immunosuppressive or other physiologic consequences that could be deleterious in various conditions. Moreover, given the considerable redundancy in proinflammatory cytokine activity, in particular between interleukin (IL)‐1 and tumor necrosis factor,7 efforts aimed at blocking a single cytokine may be