Extended lung expression and increased tissue localization of viral IL-10 with adenoviral gene therapy

Rebecca M. Minter, Maria A. Ferry, John E. Rectenwald, F. R. Bahjat, Andreas Oberholzer, Caroline Oberholzer, Drake La Face, Van Tsai, C. M. Iqbal Ahmed, Beth Hutchins, Edward M. Copeland, Harold S. Ginsberg, Lyle L. Moldawer

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26 Scopus citations

Abstract

IL-10 is a pleiotropic cytokine that acts as an important regulator of macrophage, T cell, and natural killer cell functions. Human IL-10 (hIL-10) has both stimulatory and inhibitory effects on a wide variety of cell types. Viral IL-10 (vIL-10) possesses only a subset of hIL-10's activities, predominantly its suppression of cytokine synthesis by T helper type 1 clones. In the present report, we evaluated tissue accumulation and biological activity of hIL-10 and vIL-10 in vivo in individual organs by using a first-generation adenoviral (Ad) vector administered intratracheally and intravenously. We report the observation that Ad vectors delivering vIL-10, but not hIL-10, are associated with prolonged expression in the lung (>42 days) when delivered intratracheally. In contrast, there was no prolongation in vIL-10 expression when Ad vectors were intravenously administered, although vIL-10 levels in the tissue, but not serum, were markedly increased relative to hIL-10. Moreover, we report an augmented capacity of expressed vIL-10 versus hIL-10 to suppress the acute inflammatory responses in the lung to intratracheal administration of Ad. These findings confirm fundamental differences in Ad-induced expression of vIL-10 and hIL-10 when administered to the lungs. The results further suggest that Ad vectors expressing vIL-10 may have a role as anti-inflammatory agents in the treatment of acute and chronic lung inflammation.

Original languageEnglish (US)
Pages (from-to)277-282
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number1
DOIs
StatePublished - Jan 2 2001

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    Minter, R. M., Ferry, M. A., Rectenwald, J. E., Bahjat, F. R., Oberholzer, A., Oberholzer, C., La Face, D., Tsai, V., Iqbal Ahmed, C. M., Hutchins, B., Copeland, E. M., Ginsberg, H. S., & Moldawer, L. L. (2001). Extended lung expression and increased tissue localization of viral IL-10 with adenoviral gene therapy. Proceedings of the National Academy of Sciences of the United States of America, 98(1), 277-282. https://doi.org/10.1073/pnas.98.1.277