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Role of interleukin-18 in the development of acute pulmonary injury induced by intestinal ischemia/reperfusion and its possible mechanism.
J Gastroenterol Hepatol. 2007 Feb; 22(2):253-60.JG

Abstract

BACKGROUND AND AIMS

Lung injury is an important target for the systemic inflammatory response associated with intestinal ischemia/reperfusion (I/R). In the present study, the role of interleukin (IL)-18 in the development of acute pulmonary injury induced by intestinal I/R and its possible mechanism in relation to the increased activity of inducible nitric oxide synthase and tumor necrosis factor (TNF)-alpha were investigated.

METHODS

Mice were randomly divided into three groups: normal control group without operation; sham group with sham operation; and I/R group in which mice underwent superior mesenteric artery occlusion for 30 min followed by reperfusion for 3 h. Each group received pretreatment with exogenous IL-18, anti-IL-18 neutralizing antibody or L-NIL, the selective inhibitor of inducible nitric oxide synthase, 30 min before ischemia. The expression of TNF-alpha was detected by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Lung injury was evaluated by means of Evans blue dye (EBD) concentration, myeloperoxidase (MPO) activity and morphological analysis.

RESULTS

The experimental results showed that both in the sham-operated and I/R groups of animals, pretreatment with exogenous IL-18 clearly enhanced pulmonary MPO activity, microvascular leakage and the expression of TNF-alpha mRNA and protein. In contrast, IL-18 did not increase the TNF-alpha level and degree of lung injury, although it clearly enhanced the pulmonary MPO activity in normal animals. Meanwhile, IL-18 antibody given prior to ischemia led to a reduction in the sequestration of neutrophils, extravasation of EBD and downregulation of the serum level of TNF-alpha in the I/R group of animals. In addition, selective inhibition of inducible nitric oxide synthase (iNOS) that inhibited plasma extravasation and pulmonary injury without affecting the MPO activity could be demonstrated in all treated animals.

CONCLUSIONS

These data suggested a role of IL-18 in the activation and sequestration of neutrophils in lungs. Our results were consistent with the hypothesis that increased sequestration of neutrophils and microvascular leakage might, respectively, relate to the increased IL-18 level and the elevation of TNF-alpha/iNOS activity, and these two aspects might synergically contribute to intestinal I/R-induced pulmonary dysfunction.

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Authors+Show Affiliations

Yang YJ
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Chen SH
No affiliation info available
Ge XR
No affiliation info available

MeSH

AnimalsInterleukin-18IntestinesMiceMice, Inbred C57BLReperfusion InjuryRespiratory Distress Syndrome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17295880

Citation

Yang, Yong-Jie, et al. "Role of Interleukin-18 in the Development of Acute Pulmonary Injury Induced By Intestinal Ischemia/reperfusion and Its Possible Mechanism." Journal of Gastroenterology and Hepatology, vol. 22, no. 2, 2007, pp. 253-60.
Yang YJ, Chen SH, Ge XR. Role of interleukin-18 in the development of acute pulmonary injury induced by intestinal ischemia/reperfusion and its possible mechanism. J Gastroenterol Hepatol. 2007;22(2):253-60.
Yang, Y. J., Chen, S. H., & Ge, X. R. (2007). Role of interleukin-18 in the development of acute pulmonary injury induced by intestinal ischemia/reperfusion and its possible mechanism. Journal of Gastroenterology and Hepatology, 22(2), 253-60.
Yang YJ, Chen SH, Ge XR. Role of Interleukin-18 in the Development of Acute Pulmonary Injury Induced By Intestinal Ischemia/reperfusion and Its Possible Mechanism. J Gastroenterol Hepatol. 2007;22(2):253-60. PubMed PMID: 17295880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of interleukin-18 in the development of acute pulmonary injury induced by intestinal ischemia/reperfusion and its possible mechanism. AU - Yang,Yong-Jie, AU - Chen,Song-Hua, AU - Ge,Xi-Rui, PY - 2007/2/14/pubmed PY - 2007/6/5/medline PY - 2007/2/14/entrez SP - 253 EP - 60 JF - Journal of gastroenterology and hepatology JO - J Gastroenterol Hepatol VL - 22 IS - 2 N2 - BACKGROUND AND AIMS: Lung injury is an important target for the systemic inflammatory response associated with intestinal ischemia/reperfusion (I/R). In the present study, the role of interleukin (IL)-18 in the development of acute pulmonary injury induced by intestinal I/R and its possible mechanism in relation to the increased activity of inducible nitric oxide synthase and tumor necrosis factor (TNF)-alpha were investigated. METHODS: Mice were randomly divided into three groups: normal control group without operation; sham group with sham operation; and I/R group in which mice underwent superior mesenteric artery occlusion for 30 min followed by reperfusion for 3 h. Each group received pretreatment with exogenous IL-18, anti-IL-18 neutralizing antibody or L-NIL, the selective inhibitor of inducible nitric oxide synthase, 30 min before ischemia. The expression of TNF-alpha was detected by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Lung injury was evaluated by means of Evans blue dye (EBD) concentration, myeloperoxidase (MPO) activity and morphological analysis. RESULTS: The experimental results showed that both in the sham-operated and I/R groups of animals, pretreatment with exogenous IL-18 clearly enhanced pulmonary MPO activity, microvascular leakage and the expression of TNF-alpha mRNA and protein. In contrast, IL-18 did not increase the TNF-alpha level and degree of lung injury, although it clearly enhanced the pulmonary MPO activity in normal animals. Meanwhile, IL-18 antibody given prior to ischemia led to a reduction in the sequestration of neutrophils, extravasation of EBD and downregulation of the serum level of TNF-alpha in the I/R group of animals. In addition, selective inhibition of inducible nitric oxide synthase (iNOS) that inhibited plasma extravasation and pulmonary injury without affecting the MPO activity could be demonstrated in all treated animals. CONCLUSIONS: These data suggested a role of IL-18 in the activation and sequestration of neutrophils in lungs. Our results were consistent with the hypothesis that increased sequestration of neutrophils and microvascular leakage might, respectively, relate to the increased IL-18 level and the elevation of TNF-alpha/iNOS activity, and these two aspects might synergically contribute to intestinal I/R-induced pulmonary dysfunction. SN - 0815-9319 UR - https://www.unboundmedicine.com/medline/citation/17295880/Role_of_interleukin_18_in_the_development_of_acute_pulmonary_injury_induced_by_intestinal_ischemia/reperfusion_and_its_possible_mechanism_ L2 - https://doi.org/10.1111/j.1440-1746.2006.04612.x DB - PRIME DP - Unbound Medicine ER -