Published online Apr 28, 2014. doi: 10.3748/wjg.v20.i16.4771
Revised: January 24, 2014
Accepted: March 5, 2014
Published online: April 28, 2014
Processing time: 178 Days and 19.7 Hours
AIM: To investigate whether mesenteric lymph from rats with severe intraperitoneal infection (SII) induces lung injury in healthy rats.
METHODS: Twenty adult male specific pathogen-free Wistar rats were divided into two groups. Animals in the SII group received intraperitoneal injection of Escherichia coli (E. coli) at a dose of 0.3 mL/100 g. Control rats underwent the same procedure, but were injected with normal saline rather than E. coli. We ligated and drained the mesenteric lymphatic vessels and collected the mesenteric lymph. Mesenteric lymph collected from SII or control rats was infused intravenously into male healthy rats at a rate of 1 mL/h for 4 h. At the end of the infusion, all rats were sacrificed. Lungs were removed and examined histologically, and wet-to-dry weight (W/D) ratio and myeloperoxidase (MPO) activity were determined. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the levels of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. We performed Western blot to investigate the activation of Toll-like receptor (TLR)-4, and nuclear factor (NF)-κB p65.
RESULTS: Compared with the control infusion group, there were obvious pathological changes in the SII group. The W/D ratio was significantly increased in the SII compared to control infusion group (5.86 ± 0.06 vs 5.37 ± 0.06, P < 0.01). MPO activity significantly increased in the SII infusion rats with a mean level of 0.86 ± 0.02 U/g compared to 0.18 ± 0.05 U/g in the control group (P < 0.01). The concentrations of TNF-α and IL-6 were significantly increased in the SII infusion group. The concentration of TNF-α was significantly increased in the SII infusion rats compared to control infusion rats (2104.46 ± 245.91 vs 1475.13 ± 137.82 pg/mL, P < 0.01). The concentration of IL-6 was significantly increased in the SII infusion rats with a mean level of 50.56 ± 2.85 pg/mL compared to 43.29 ± 2.02 pg/mL (P < 0.01). The expression levels of TLR-4 (7496.68 ± 376.43 vs 4589.02 ± 233.16, P < 0.01) and NF-κB (8722.19 ± 323.96 vs 6498.91 ± 338.76, P < 0.01) were significantly increased in the SII infusion group compared to the control infusion group. The infusion of SII lymph, but not control lymph, caused lung injury.
CONCLUSION: The results indicate that SII lymph is sufficient to induce acute lung injury.
Core tip: We previously speculated that the lymphatic pathway plays a leading role in the early lung injury caused by severe intraperitoneal infection (SII), and that the mesenteric lymph may be the original source of organ damage. Here, we infused mesenteric lymph from rats with SII into healthy rats to investigate the effect on lung tissues. We confirmed that the damage to the remote organ was caused via the mesenteric lymphatic pathway.