Glutamine Administration Attenuates Poly(I:C)-Induced Lung Injury by Reducing Neutrophil Infiltration and Activating the TLR-3 Antiviral Pathway

Objectives: In this study, we investigated the effects of intravenous glutamine (GLN) administration on the Toll-like receptor 3 (TLR3) antiviral pathway and leukocyte migration in mice with poly(I:C)-induced acute lung injury (ALI). Methods: There were four groups in this study: the NC group, mice without an intratracheal injection; the SH group, mice intratracheally injected with endotoxin-free saline; the PS group, intratracheally instilled with 3 mg poly(I:C)/kg body weight (BW), followed by an intravenous (IV) injection of saline; and the PG group, intratracheally injected with poly(I:C) followed by the IV administration of 0.75 g GLN/kg BW. Mice in the SH, PS, and PG groups were sacrificed at 4, 12, and 24 h after intratracheal instillation. Results: The results showed that poly(I:C) stimulation decreased the plasma GLN concentration and increased inflammatory cytokine levels. In bronchoalveolar lavage fluid, concentrations of interferon λ3 and percentages of macrophages and M1 macrophages decreased, while neutrophils increased along with significantly elevated myeloperoxidase activity in lung tissues. The gene expressions of molecules related to leukocyte migration increased, whereas tight/adherens junction expressions in endothelial and epithelial cells were reduced. GLN supplementation upregulated the mRNA and/or protein expressions of TLR3 antiviral pathway-related factors and tight/adherens junctions while reducing inflammatory cytokines and the expressions of leukocyte migration molecules. Histological results also showed that lung injury was attenuated. Conclusions: These findings indicated that intravenous GLN administration after poly(I:C) instillation restored plasma GLN levels and alleviated ALI by activating the TLR3 antiviral pathway, suppressing leukocyte migration and neutrophil infiltration, mitigating inflammation, and improving the integrity of the alveolar–capillary barrier.