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A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infection.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 2/3/2009, Vol. 106 Issue 5, p1560-1565, 6p, 1 Chart, 5 Graphs
- Publication Year :
- 2009
-
Abstract
- Pulmonary tissue damage resulting from influenza virus infection is caused by both the cytolytic activity of the, virus and the host immune response. Immune-mediated injury results from T cell-mediated destruction of virus-infected cells and by release of cytokines and chemokines that attract polymorphonuclear leukocytes (PML) and macrophages to the infected site. The cytokines/chemokines potentiate dendritic cell (DC) activation and T cell expansion, which further enhances local damage. Here we report that immune modulation by local administration to the respiratory tract of sphingosine analog AAL-R significantly dampens the release of cytokines and chemokines while maintaining protective neutralizing antibody and cytotoxic T cell responses. As a result there was a marked reduction of infiltrating PML and macrophages into the lung and resultant pulmonary tissue injury. DC maturation was suppressed, which limited proliferation of specific antiviral T cells in the lung and draining lymph nodes. Further, AAL-R was effective in controlling CD8<superscript>+</superscript> T cell accumulation in the lungs even when given 4 days after initiation of influenza virus infection. These data indicate that sphingosine analogs display useful potential for controlling the immunopathology caused by influenza virus. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 106
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 36618747
- Full Text :
- https://doi.org/10.1073/pnas.0812689106