Effects of early enteral nutrition on Th17/Treg cells and IL-23/IL-17 in septic patients

Abstract

Background: The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients; however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL-23/IL-17 axis.

Aim: To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients.

Methods: In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded.

Results: Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission (P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group (P < 0.05). However, no difference in the 28-d mortality was found between the two groups (P = 0.728).

Conclusion: EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL-23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients.

Keywords: Early enteral nutrition; Enteral nutrition; IL-23/IL-17 axis; Sepsis; T helper lymphocytes; Th17/Treg cells.

Figure 1

Flow diagram of the participants.

Figure 2

Difference in the Th17 and Treg lymphocyte percentages and the Th17/Treg cell ratios between the early enteral nutrition and delayed enteral nutrition groups. A: Difference in the Th17 lymphocyte percentages between the early enteral nutrition (EEN) and delayed enteral nutrition (DEN) groups; B: Difference in the Treg lymphocyte percentages between the EEN and DEN groups; C: Differences in the Th17/Treg cell ratios between the EEN and DEN groups. ^aP < 0.05. EEN: Early enteral nutrition; DEN: Delayed enteral nutrition.

Figure 3

Difference in the serum IL-17 and IL-23 levels and the IL-23/IL-17 ratios between the early enteral nutrition and delayed enteral nutrition groups. A: Difference in the serum IL-17 levels between the early enteral nutrition (EEN) and delayed enteral nutrition (DEN) groups; B: Difference in the serum IL-23 levels between the EEN and DEN groups; C: Difference in the IL-23/IL-17 ratios between the EEN and DEN groups. ^aP < 0.05. EEN: Early enteral nutrition; DEN: Delayed enteral nutrition.

Figure 4

Difference in the serum IL-6 and IL-10 levels between the early enteral nutrition and delayed enteral nutrition groups. A: Difference in the serum IL-6 levels between the early enteral nutrition (EEN) and delayed enteral nutrition (DEN) groups; B: Difference in the serum IL-10 levels between the EEN and DEN groups. ^aP < 0.05. EEN: Early enteral nutrition; DEN: Delayed enteral nutrition.

Figure 5

Survival curves for up to 28 days after admission between the early enteral nutrition and delayed enteral nutrition groups (P = 0.728). EEN: Early enteral nutrition; DEN: Delayed enteral nutrition.