Intra-articular IL-10 gene transfer regulates the expression of collagen-induced arthritis (CIA) in the knee and ipsilateral paw

We studied the effects of local IL-10 application, introduced by a recombin ant human type 5 adenovirus vector, in the mouse knee joint during the earl y phase of CIA. One intra-articular injection with the IL-10-expressing vir us (Ad5E1mIL-10) caused substantial over-expression of IL-10 in the mouse k nee joint, using virus dosages which did not induce distracting inflammatio n. High expression of IL-10 was noted for a few days, being maximal at day 1. One intra-articular injection of Ad5E1mIL-10 in the knee joints of colla gen type II (CII)-immunized mice, before onset of CIA was noted, reduced th e incidence of collagen arthritis in that knee. Of high interest, the prote ctive effect of local IL-10 expression by Ad5E1mIL-10 was not restricted to the knee joint alone. The arthritis incidence in the ipsilateral paw was h ighly suppressed. In contrast, local IL-10 over-expression was not effectiv e when treatment was started after onset of CIA. Further analysis in the ac ute streptococcal cell wall-induced arthritis model revealed that local IL- 10 over-expression markedly suppressed the production of tumour necrosis fa ctor-alpha (TNF-alpha) and IL-1 alpha, but had no significant effect on IL- 1 beta and IL-12 production in the inflamed synovium. These data indicate t hat local over-expression of IL-10 in the knee joint of mice regulates the expression of collagen arthritis, probably through down-regulation of TNF-a lpha.