Antecedent Administration of Glutamine Benefits the Homeostasis of CD4⁺ T Cells and Attenuates Lung Injury in Mice With Gut-Derived Polymicrobial Sepsis

Background: Sepsis is a syndrome with CD4⁺ T-cell dysfunction and dysregulation of T helper (Th) and regulatory T (Treg) cells. Glutamine (Gln) is a nutrient with immunomodulatory properties. This study investigated the effects of dietary Gln pretreatment on Th and Treg cell homeostasis and lung injury in mice with gut-derived polymicrobial sepsis. Methods: Mice were randomly assigned to 4 groups with 2 control (C and G) and 2 sepsis groups (SC and SG). The C and SC groups were fed a common semipurified diet, whereas the G and SG groups received an identical diet except that part of the casein was replaced by Gln. Mice were administered these diets for 2 weeks. Then mice in the control groups underwent a sham operation, whereas operations in the sepsis groups were performed with cecal ligation and puncture. Mice were killed 24 hours after the surgery. Blood, spleens, and lungs were collected for further examination. Results: Sepsis resulted in a decreased blood T-lymphocyte percentage, whereas percentages of interferon-γ-expressing, interleukin (IL)-4-expressing, and IL-17-expressing CD4⁺ T cells were upregulated. Compared with the SC group, Gln administration before sepsis reduced blood Th1, Th2, and Th17 but increased Treg percentages. Also, percentages of CD69-expressing CD4⁺ and CD8⁺ cells in the spleen increased. Concomitant with the decreased plasma IL-6 and keratinocyte-derived chemokine levels, the SG group exhibited a lower injury score of the lungs. Conclusions: Pretreatment with Gln may elicit more balanced Th polarization, alleviate inflammatory response, and attenuate lung injury induced by polymicrobial sepsis.