Lipid-rich enteral nutrition improves the defense against an opportunistic infection during polymicrobial sepsis

Abstract

The development of an immunosuppressive state during the protracted course of sepsis is associated with opportunistic infections and is considered to correlate with the extent of the proinflammatory response during early sepsis. Short-term intervention with enteral lipid-rich nutrition was shown to attenuate the acute inflammatory response. This study investigates the effects of lipid-rich nutrition on the immunosuppression induced by polymicrobial sepsis. Female BALB/c mice were either fasted or fed liquid lipid-rich nutrition or isocaloric control nutrition before and shortly after induction of polymicrobial sepsis through cecal ligation and puncture (CLP) or sham operation. After 4 days, mice were intranasally infected with Pseudomonas aeruginosa. Twenty-four hours after P. aeruginosa infection, fasted and control nutrition-fed CLP mice displayed a significantly higher bacterial load in the lungs than did corresponding sham-operated mice (P < 0.001 and P < 0.05, respectively). Fasted CLP mice expressed reduced pulmonary levels of proinflammatory cytokines interleukin 12 (IL-12) and interferon γ (IFN-γ) in comparison to sham mice (both P < 0.05). Lipid-rich nutrition prevented the increase in bacteria, promoted the IL-12 and IFN-γ production (IL-12 and IFN-γ [P < 0.05] vs. fasted and IFN-γ [P < 0.05] vs. control nutrition), and prevented the expression of the immunosuppressive cytokine IL-10 (P < 0.05 vs. control nutrition) in lungs of CLP mice. The preserved immune defense during late sepsis in lipid-rich fed mice was preceded by attenuation of the early inflammatory response (IL-6 [P = 0.05] and IL-10 [P < 0.01] vs. fasted CLP mice) at 6 h after CLP. In conclusion, short-term treatment with lipid-rich enteral nutrition improves the pulmonary antimicrobial defense during polymicrobial sepsis.