Abstract
Despite sound basis to suspect that aggressive and early administration of nutritional support may hold therapeutic benefits during sepsis, recommendations for nutritional support have been somewhat underwhelming. Current guidelines (ESPEN and ASPEN) recognise a lack of clear evidence demonstrating the beneficial effect of nutritional support during sepsis, raising the question: why, given the perceived low efficacy of nutritionals support, are there no high-quality clinical trials on the efficacy of permissive underfeeding in sepsis? Here, we review clinically relevant beneficial effects of permissive underfeeding, motivating the urgent need to investigate the clinical benefits of delaying nutritional support during sepsis.
Highlights
Despite sound basis to suspect that aggressive and early administration of nutritional support may hold therapeutic benefits during sepsis, recommendations for nutritional support have been somewhat underwhelming
We have previously argued that a pre-existing catabolic state may be adaptive [35]: since degradation processes are already in full swing in cells exhibiting a catabolic state, intracellular pathogens would be confronted with a narrow window of opportunity to engage countermeasures
Peptides loaded on MHC I are typically in 8–12 amino acids in length; MHC II are between 14 and 20 [37]. This implies that the autophagic processing of proteins for presentation on MHC II may alter the immunogenicity of potentially infected cells. In support of this possibility, it was recently shown that treatment of cancer cells with IFN-γ altered the processing and length of peptides loaded on MHC proteins [38]: since IFN-γ is a potent inducer of autophagy [39], it is possible that autophagy may alter the immunogenicity of epitopes expressed by cells, rendering infected cells more visible to the immune system
Summary
Despite sound basis to suspect that aggressive and early administration of nutritional support may hold therapeutic benefits during sepsis, recommendations for nutritional support have been somewhat underwhelming. It is generally advised, based on expert consensus, extrapolation from other critical care settings, or through reference to pre-clinical findings in studies of varying quality, that early enteral nutritional support may be beneficial. Macro-autophagy (hereafter autophagy) is an evolutionarily conserved catabolic process that plays an essential role in promoting cell survival [20].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
