Co-administration of N-acetylcysteine and dexmedetomidine plays a synergistic effect on protection of LPS-induced acute lung injury via correcting Th1/Th2/Th17 cytokines imbalance.

Recently both N-acetylcysteine (NAC) and Dexmedetomidine (DEX) have shown emerging roles in protection of acute lung injury (ALI). However, how their protective roles work and whether they can provide synergistic effects in ALI remain unknown. Here we explored it from the hot research viewpoint of Th1/Th2/Th17 cytokines balance. Lipopolysaccharide (LPS)-induced ALI was established and treated with NAC and/or DEX. Mice were divided into Sham group, ALI group, NAC group, DEX group and NAC+DEX group. Mice were sampled at 6, 12 and 24 hours after the model construction. Histopathology, wet to dry ratio and myeloperoxidase (MPO) activity were assessed in lung tissues. Protein concentration and cell count were assessed in bronchoalveolar lavage fluid (BALF). Th1/Th2/Th17 cytokines were assessed in plasma, BALF and lung homogenate. ALI-induced lung morphological damage, edema and aberrant MPO activity can be attenuated by NAC or DEX and mostly by NAC+DEX. NAC with DEX significantly reduced ALI-induced protein leakage and cell infiltration in BALF. Th1/Th2/Th17 cytokines imbalance aggravated with ALI progression. NAC, DEX and especially NAC+DEX can effectively correct these unbalanced cytokines. Galectin-9 and Tim-3 were transcriptionally up-regulated in ALI. Combination of NAC with DEX obtained a maximum effect on decreasing Galectin-9/Tim-3 expression. In summary, Th1/Th2/Th17 cytokines imbalance is newly found to participate in LPS-induced ALI. NAC or DEX administration can attenuate ALI by rebalancing Th1/Th2/Th17 cytokines. Their protective roles can be enhanced when co-administration, because DEX may relieve the Galectin-9/Tim-3 axis-mediated immune suppression.