부산대학교 도서관

Targeted expression of interleukin-10 (IL-10) has been proposed as a means to suppress acute and chronic inflammation. We explored the capacity of targeted adenoviral expression of human or viral IL-10 to improve outcome in a zymosan-induced model of acute lung injury and multisystem organ failure. Intratracheal administration of adenovirus expressing either human or viral IL-10 prior to zymosan administration significantly improved survival at a dose of 107 particles (P<0.01), whereas the same recombinant vectors were ineffective at 108 particles and increased mortality at 109 particles. Improved survival after administration of 107 particles of adenovirus expressing viral or human IL-10 was associated with local tissue expression of IL-10 (100–300 pg/g wet wt). In contrast, mortality after administration of 109 particles was associated with markedly elevated IL-10 expression, both in the lung (10 000–70 000 pg/g wet wt) and systemically (1000–3000 pg/ml plasma), with evidence of an exaggerated systemic inflammatory response (plasma IL-6 and TNFα). Targeted gene expression of IL-10 can be used to treat acute inflammatory processes, but increased doses resulting in its systemic release are not associated with improvements in outcome, and may actually exacerbate acute inflammatory processes.Gene Therapy (2006) 13, 276–282. doi:10.1038/sj.gt.3302600; published online 27 October 2005 [ABSTRACT FROM AUTHOR]