Inhibition of Endotoxin-Induced Lung Inflammation by Interleukin-10 Gene Transfer in Mice

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Dokka S ; Malanga CJ ; Rojanasakul Y ; Shi X
• Description:
  Interleukin (IL)-10 is an anti-inflammatory cytokine that has great potential for use in the treatment of inflammatory and immune illnesses. In this study, gene transfer was used to induce IL-10 transgene expression in murine lungs for treatment of endotoxin-induced lung inflammation. Gene transfer was performed with a cytomegalovirus (CMV)-IL-10 plasmid with the aid of the liposomal agents LipofectAMINE and N-[1-(2,3-dioleoyl)propyl]-N,N, N-trimethylammonium methylsulfate (DOTAP). Administration of the endotoxin caused a marked increase in lung inflammation as indicated by increased tumor necrosis factor (TNF)-alpha release and neutrophil count. Pretreatment of the mice with IL-10 plasmid with and without LipofectAMINE had no inhibitory effect on lung inflammation and IL-10 transgene expression. LipofectAMINE by itself induced lung inflammation, an effect that was not observed with DOTAP. IL-10 plasmid when codelivered with DOTAP expressed biologically active IL-10 protein and caused a reduction in endotoxin-induced inflammation. Transgene expression was observed as early as 3 h after administration, peaked at 12 h, and declined thereafter. We conclude that IL-10 gene transfer is a feasible approach for the treatment of lung inflammation. [Description provided by NIOSH]
• Subjects:
  Animals Endotoxins Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Author Keywords: Tumor Necrosis Factor-a Gene Transfer Laboratory Animals Liposome Lung Disorders Lung Irritants Pulmonary System Disorders Respiratory System Disorders
• ISSN:
  1040-0605
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  279
• Issue:
  5
• NIOSHTIC Number:
  nn:20020654
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2000 Nov; 279(5):L872-L877
• Contact Point Address:
  Y. Rojanasakul, West Virginia University School of Pharmacy, Department of Basic Pharmaceutical Sciences, PO Box 9530, Morgantown, WV 26506
• Email:
  yrojanasakul@hsc.wvu.edu
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:30e29401f7d7f0dc41a6025534df735697357b23de499d2d551b029d6c17c3ea45cac9ff647c6b71e090a55dc2839690cbedf9cc1e28e0573f4e96782e9407b9
• Download URL:
  https://stacks.cdc.gov/view/cdc/198338/cdc_198338_DS1.pdf
• File Type:
  [PDF - 147.56 KB ]