Antisense IL-10 abrogates the inhibitory effects of IL-10 production by transfected tumor cells

Interleukin-10 (IL-10) is a pleiotropic cytokine that has a variety of down regulatory effects on immunologic and inflammatory processes. Ectopic tumor expression of IL-10 inhibited tumor growth, and local administration of an tisense IL-10 significantly reversed the effects of IL-10 transfection in P 815 mastocytoma. Tissue inhibitors of metalloproteinase (TIMPs) have been a ssociated with decreased tumorigenesis and reduced metastasis, and TIMPs we re increased in the region surrounding P815/IL-10 tumors and reduced in ant isense IL-10-treated mice. in addition, the antisense IL-10 group had the l argest tumor volume and poorest survival when compared with the P815/IL-10 control or sense groups. In summary, our data suggest that, in a mouse mode l, antisense IL-10 has substantive effects in reducing IL-10 translation an d inhibiting IL-10-mediated TIMP upregulation, and, by doing so, allows IL- 10-transfected mastocytoma to grow unchecked. Thus, ectopic tumor expressio n of IL-10 inhibits tumor growth, and antisense IL-10 administration in viv o reverses this protective effect.