Intravenous infusion of mesenteric lymph from severe intraperitoneal infection rats causes lung injury in healthy rats.
OBJECTIVE
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.


CONCLUSIONS
The results indicate that SII lymph is sufficient to induce acute lung injury.
Yan-Min Zhang, Tianjin Medical University, Intensive Care Unit, Tianjin Nankai Hospital, Tianjin 300100, China.
Yan-Min
YM
Zhang
Yan-Min Zhang, Tianjin Medical University, Intensive Care Unit, Tianjin Nankai Hospital, Tianjin 300100, China.
Shu-Kun
SK
Zhang
Yan-Min Zhang, Tianjin Medical University, Intensive Care Unit, Tianjin Nankai Hospital, Tianjin 300100, China.
Nai-Qiang
NQ
Cui
D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D018836:Inflammation Mediators / Q000378:metabolism; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008196:Lymph / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D010538:Peritonitis / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism / Q000382:microbiology; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism* / Q000382:microbiology; D012720:Severity of Illness Index; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018836:Inflammation Mediators; D015850:Interleukin-6; C498145:Rela protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase
Acute lung injury; Mesenteric lymph; Nuclear factor κB; Severe intraperitoneal infection; Toll-like receptor 4