Effects of glutamine and n-3 polyunsaturated fatty acid mixed lipid emulsion supplementation of parenteral nutrition on sepsis score and bacterial clearance in early experimental sepsis

Abstract

Glutamine (GLN) and n-3 polyunsaturated fatty acids (n-3PUFAs) have been shown to potentially possess immune-modulating and disease-modifying properties in experimental and clinical critical illness when given with parenteral nutrition (PN). However, we recently showed in experimental cancer models that combinations of GLN/n-3 PUFA may antagonize benefits of either nutrient alone. Thus, our aim was to explore the effects of PN-containing GLN and n-3PUFA mixed lipid emulsion (MLE) alone and in combination in experimental sepsis. Adult male rats were exposed to cecal ligation and puncture (CLP) and sacrificed at 24h. Rats were infused with either normal saline (NS); PN+Intralipid (PNcont); PN+GLN; PN+n-3PUFA MLE; or PN+GLN/n-3PUFA MLE after CLP-sepsis for 23h. Animals were assessed at 24h for sepsis score, Gram (+) and Gram (-) bacterial load in blood, peritoneum, and bronchoalveolar lavage fluid (BALF). Rats treated with PN+GLN or PN+n-3PUFA showed significantly lower sepsis scores compared to NS and PNcont (all p≤0.016). Non-significant trends to improved sepsis scores was observed in rats treated with PN+GLN/n-3PUFA versus NS (p=0.067) or PNcont (p=0.093). Rats treated with PN+GLN, PN+n-3PUFA, or PN+GLN/n-3PUFA had significant improvement or trends to improved Gram (+) and Gram (-) bacterial loads in BALF versus NS (p≤0.05, PN+GLN and PN+GLN/n-3PUFA for Gram (+); p=0.057, PN+n-3PUFA for Gram (+); p≤0.05, n-3PUFA and PN+GLN/n-3PUFA for Gram (-)). No differences between groups in blood or peritoneal bacterial counts observed. This data describes initial evidence that nutritional-doses of GLN, n-3PUFA MLE, and GLN+n-3PUFA MLE in PN can improve bacterial load/clearance in sepsis. Further, improvements of sepsis score by PN+n-3PUFA MLE and PN+GLN was observed. Previously observed antagonism of benefits of PN-containing GLN or n-3PUFAs alone by combinations of these nutrients was not observed in experimental sepsis. These results suggest further research is needed into PN-strategies using GLN and/or n-3PUFA at nutritional-doses in sepsis.