Enteral nutrition (EN) is widely used in intensive care units around the world, but the optimal dosing strategy during the first week of critical illness is still controversial. Numerous studies in the past decade have provided conflicting recommendations regarding the roles of trophic and permissive/intentional underfeeding strategies. Further complicating effective medical decision making is the widespread, yet unintentional and persistent underdelivery of prescribed energy and protein, in addition to the trend for recommending ever-higher amounts of protein delivery. We postulate that the key to appropriate enteral strategy lies within an accurate and patient-specific assessment. Patients with a baseline high nutrition risk and those with increased nutrition demands, such as those with wounds, surgery, or burns, likely require full nutrition support, in contrast with medical patients, such as those with acute respiratory distress syndrome, who may selectively be appropriate for trophic strategies. In this analysis, we review several key trials for and against full EN in the first week of critical illness, as well as key issues such as the role of autophagy and immunonutrition in enteral dose selection.
Interleukin‐2 (IL‐2) is a cytokine critical to normal immune function. Our laboratory has shown that IL‐2 is retained in tissues by heparan sulfate (HS). While known as a monomer, a dimeric form of IL‐2 was previously identified in fish optic neurons, and this form was toxic to oligodendrocytes. Given this observation, we asked whether dimeric IL‐2 is found in mammalian tissues. Murine and human aorta and kidney were assessed by Western blot for the presence of IL‐2. Dimeric (30 kD) IL‐2 was identified in each tissue. Heparinase digestion of tissues liberated dimeric IL‐2, suggesting that the dimer is bound, at least in part, by HS. To ascertain whether dimeric IL‐2 is cytotoxic, we treated cultures of renal epithelial cells with increasing concentrations of dimeric IL‐2, isolated by electroelution. Signs of cytotoxicity were evident within 15 minutes of dimer addition. Commercial IL‐2, isolated identically to dimeric IL‐2, was not cytotoxic. Systemic administration to mice of 10 μg of dimeric IL‐2 induced vacuolization of renal epithelium, a morphology typically seen with ischemic injury. Finally, murine kidneys subjected to 60 minutes of ischemia, compared to sham controls, expressed greatly increased amounts of dimeric IL‐2 in tissue homogenates. These results suggest that dimeric IL‐2 may contribute to acute tubular necrosis and, in turn, renal dysfunction. This work was supported by institutional funds.
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