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

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.

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Cite this paper

@article{Minter2001ExtendedLE, title={Extended lung expression and increased tissue localization of viral IL-10 with adenoviral gene therapy.}, author={Rebecca M. Minter and Matthew A. Ferry and John E Rectenwald and Frances Rena Bahjat and Andreas Oberholzer and Caroline Oberholzer and Drake La Face and Van Tsai and Chulbul M. I. Ahmed and Beth Hutchins and Edward M . Copeland and Harold S. Ginsberg and Lyle L. Moldawer}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2001}, volume={98 1}, pages={277-82} }