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

INTRODUCTION: 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. METHODS: Adult male rats were exposed to cecal ligation and puncture (CLP) and sacrificed at 24 h. 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 23 h. Animals were assessed at 24 h for sepsis score, Gram (+) and Gram (-) bacterial load in blood, peritoneum, and bronchoalveolar lavage fluid (BALF). RESULTS: 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. CONCLUSIONS: 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.