Tags

Type your tag names separated by a space and hit enter

The role of proinflammatory cytokines in lung ischemia-reperfusion injury.
J Thorac Cardiovasc Surg. 2003 Feb; 125(2):261-72.JT

Abstract

OBJECTIVE

Proinflammatory cytokines are known to play roles in ischemia-reperfusion injury of the heart, kidney, small bowel, skin, and liver. Little is known about their roles in ischemia-reperfusion injury of the lung. This study was undertaken to define the role of 2 proinflammatory cytokines, tumor necrosis factor alpha and interleukin 1beta, in ischemia-reperfusion injury of the lung.

METHODS

Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received anti-tumor necrosis factor alpha or anti-interleukin 1beta antibody before reperfusion. Increased vascular permeability in the lung was measured by using iodine 125-labeled bovine serum albumin. Neutrophil sequestration in the lung parenchyma was determined on the basis of activity. Bronchoalveolar lavage was performed to measure cell counts. Separate tissue samples were processed for histology, cytokine protein, and messenger RNA content by using Western blotting and the ribonuclease protection assay.

RESULTS

Animals receiving anti-tumor necrosis factor alpha and anti-interleukin 1beta demonstrated reduced injury compared with that seen in positive control animals (vascular permeability of 48.7% and 29.4% lower, respectively; P <.001). Vascular injury was reduced by 71% when antibodies to tumor necrosis factor alpha and interleukin 1beta were administered together. Lung neutrophil accumulation was markedly reduced among animals receiving anti-tumor necrosis factor alpha and anti-interleukin 1beta (myeloperoxidase content of 30.9% and 38.5% lower, respectively; P <.04) and combination blockade afforded even greater protection (52.4% decrease, P <.01). Bronchoalveolar lavage leukocyte content was also reduced by treatment with anti-tumor necrosis factor alpha, anti-interleukin 1beta, and combination treatment. Reductions in permeability, myeloperoxidase, and bronchoalveolar lavage leukocyte content also resulted in a decrease in a histologic injury. Finally, anti-tumor necrosis factor alpha and anti-interleukin 1beta treatment resulted in decreased messenger RNA expression for a number of early response and regulatory cytokines.

CONCLUSION

Tumor necrosis factor alpha and interleukin 1beta help regulate the development of lung ischemia-reperfusion injury. They appear to promote injury by altering expression of proinflammatory and anti-inflammatory cytokines and influencing tissue neutrophil recruitment.

Authors+Show Affiliations

Division of Cardiothoracic Surgery, University of Washington, Seattle, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12579094

Citation

Krishnadasan, Baiya, et al. "The Role of Proinflammatory Cytokines in Lung Ischemia-reperfusion Injury." The Journal of Thoracic and Cardiovascular Surgery, vol. 125, no. 2, 2003, pp. 261-72.
Krishnadasan B, Naidu BV, Byrne K, et al. The role of proinflammatory cytokines in lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg. 2003;125(2):261-72.
Krishnadasan, B., Naidu, B. V., Byrne, K., Fraga, C., Verrier, E. D., & Mulligan, M. S. (2003). The role of proinflammatory cytokines in lung ischemia-reperfusion injury. The Journal of Thoracic and Cardiovascular Surgery, 125(2), 261-72.
Krishnadasan B, et al. The Role of Proinflammatory Cytokines in Lung Ischemia-reperfusion Injury. J Thorac Cardiovasc Surg. 2003;125(2):261-72. PubMed PMID: 12579094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of proinflammatory cytokines in lung ischemia-reperfusion injury. AU - Krishnadasan,Baiya, AU - Naidu,Babu V, AU - Byrne,Karen, AU - Fraga,Charles, AU - Verrier,Edward D, AU - Mulligan,Michael S, PY - 2003/2/13/pubmed PY - 2003/3/21/medline PY - 2003/2/13/entrez SP - 261 EP - 72 JF - The Journal of thoracic and cardiovascular surgery JO - J Thorac Cardiovasc Surg VL - 125 IS - 2 N2 - OBJECTIVE: Proinflammatory cytokines are known to play roles in ischemia-reperfusion injury of the heart, kidney, small bowel, skin, and liver. Little is known about their roles in ischemia-reperfusion injury of the lung. This study was undertaken to define the role of 2 proinflammatory cytokines, tumor necrosis factor alpha and interleukin 1beta, in ischemia-reperfusion injury of the lung. METHODS: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received anti-tumor necrosis factor alpha or anti-interleukin 1beta antibody before reperfusion. Increased vascular permeability in the lung was measured by using iodine 125-labeled bovine serum albumin. Neutrophil sequestration in the lung parenchyma was determined on the basis of activity. Bronchoalveolar lavage was performed to measure cell counts. Separate tissue samples were processed for histology, cytokine protein, and messenger RNA content by using Western blotting and the ribonuclease protection assay. RESULTS: Animals receiving anti-tumor necrosis factor alpha and anti-interleukin 1beta demonstrated reduced injury compared with that seen in positive control animals (vascular permeability of 48.7% and 29.4% lower, respectively; P <.001). Vascular injury was reduced by 71% when antibodies to tumor necrosis factor alpha and interleukin 1beta were administered together. Lung neutrophil accumulation was markedly reduced among animals receiving anti-tumor necrosis factor alpha and anti-interleukin 1beta (myeloperoxidase content of 30.9% and 38.5% lower, respectively; P <.04) and combination blockade afforded even greater protection (52.4% decrease, P <.01). Bronchoalveolar lavage leukocyte content was also reduced by treatment with anti-tumor necrosis factor alpha, anti-interleukin 1beta, and combination treatment. Reductions in permeability, myeloperoxidase, and bronchoalveolar lavage leukocyte content also resulted in a decrease in a histologic injury. Finally, anti-tumor necrosis factor alpha and anti-interleukin 1beta treatment resulted in decreased messenger RNA expression for a number of early response and regulatory cytokines. CONCLUSION: Tumor necrosis factor alpha and interleukin 1beta help regulate the development of lung ischemia-reperfusion injury. They appear to promote injury by altering expression of proinflammatory and anti-inflammatory cytokines and influencing tissue neutrophil recruitment. SN - 0022-5223 UR - https://www.unboundmedicine.com/medline/citation/12579094/The_role_of_proinflammatory_cytokines_in_lung_ischemia_reperfusion_injury_ DB - PRIME DP - Unbound Medicine ER -