Glutamine Modulates Sepsis-Induced Changes to Intestinal Intraepithelial γδT Lymphocyte Expression in Mice

This study investigated the effect of glutamine (GLN) on intestinal intraepithelial lymphocyte (IEL) γδT-cell cytokines and immune regulatory factor gene expressions in a mouse model of polymicrobial sepsis. Mice were randomly assigned to a normal group, a sepsis with saline (SS) group, or a sepsis with GLN (SG) group. All mice were fed a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The SS group was injected with saline, and the SG group was given 0.75 g GLN/kg body weight once via a tail vein 1 h after CLP. Septic mice were killed 12 h after CLP, and IEL γδT cells of the animals were isolated for further analysis. Results showed that compared with normal mice, sepsis resulted in lower IEL γδT-cell percentage and higher messenger RNA expressions of interferon γ, tumor necrosis factor α, interleukin 4 (IL-4), IL-13, IL-17, retinoid acid receptor–related orphan receptor γt, and complement 5a receptor by IEL γδT cells. These immunomodulatory mediator genes exhibited decreases, whereas IL-7 receptor expression increased in IEL γδT cells in septic mice with GLN administration. Annexin V/7-amino-actinomycin D stain revealed significantly lower rates of apoptosis, and IEL γδT-cell percentage was higher in the SG group. The histological findings also showed that damage to intestinal epithelial cells was less severe in the SG group. These results indicated that a single dose of GLN administered as treatment after the initiation of sepsis prevented apoptosis of IEL γδT cells and downregulated γδT cell–expressed inflammatory mediators that may consequently ameliorate the severity of sepsis-induced intestinal epithelial injury.