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

IL-10 is a pleiotropic cytokine that acts as an important regulator of macr ophage, 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. V iral IL-10 (vIL-10) possesses only a subset of hIL-10's activities, predomi nantly its suppression of cytokine synthesis by T helper type 1 clones. In the present report, we evaluated tissue accumulation and biological activit y of hIL-10 and vIL-10 in vivo in individual organs by using a first-genera tion adenoviral (Ad) vector administered intratracheally and intravenously. We report the observation that Ad vectors delivering vIL-10, but not hIL-1 0, are associated with prolonged expression in the lung (>42 days) when del ivered intratracheally. In contrast, there was no prolongation in vIL-10 ex pression when Ad vectors were intravenously administered, although vIL-10 l evels in the tissue, but not serum, were markedly increased relative to hIL -10. Moreover, we report an augmented capacity of expressed vIL-10 versus h IL-10 to suppress the acute inflammatory responses in the lung to intratrac heal administration of Ad. These findings confirm fundamental differences i n 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.