| Autor: |
J E, Shellito, M, quan Zheng, P, Ye, S, Ruan, M K, Shean, J, Kolls |
| Rok vydání: |
2001 |
| Předmět: |
|
| Zdroj: |
Alcoholism, clinical and experimental research. 25(6) |
| ISSN: |
0145-6008 |
| Popis: |
A link between alcohol abuse and bacterial pneumonia has been recognized for centuries, but mechanisms to explain this relationship are unclarified. Interleukin-17 (IL-17) is a lymphocyte-derived cytokine that is part of the inflammatory cytokine cascade. Previous studies from our laboratory indicated that IL-17 is released in lung tissue in a murine model of bacterial pneumonia caused by Klebsiella pneumoniae. The effects of alcohol consumption on pulmonary release of IL-17 are unknown.Mice were maintained on 20% ethanol in drinking water or on a control diet without alcohol. After 2 weeks, alcohol and control mice were challenged with intratracheal K. pneumoniae. Mice were followed for survival after bacterial challenge, neutrophil recruitment was assayed as myeloperoxidase, and IL-17 was measured in lung lavage fluid by enzyme-linked immunosorbent assay. In additional experiments, splenocytes from control mice were incubated with ethanol in vitro, and release of IL-17 was measured in culture supernatants. Finally, control and alcohol mice received intrapulmonary gene transfer of E-1-deleted adenovirus containing the murine IL-17 gene. These mice were then challenged with K. pneumoniae and followed for survival and neutrophil recruitment.In these studies, we demonstrate that a 2-week history of ethanol consumption in mice suppresses release of IL-17 into lung tissue, decreases neutrophil recruitment, and increases mortality from experimental K. pneumonia. In vitro experiments confirm a direct suppressive effect of ethanol on the release of IL-17 from splenocytes. In vivo administration of the IL-17 gene in an adenoviral vector to alcohol-consuming mice results in release of IL-17 into lavage fluid and normalizes neutrophil recruitment and mortality after bacterial challenge.The results of these experiments strongly implicate IL-17 as an important pathway for the immunosuppression associated with alcohol abuse and support gene therapeutic approaches to augment immune function in the alcoholic host or to treat infections associated with alcoholism. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Plný text