Interleukin-10 (IL-10) is central in immune downregulation, but so far its use in inflammatory diseases remains cumbersome. For treatment of inflammatory bowel disease, adequate amounts of IL-10 must reach the intestinal lining. Systemic injection of a pharmacologically active doses of recombinant human (rh) IL-10 results in very low mucosal levels of protein and severe toxicity and side effects. In animal models, topical and active delivery of IL-10 by ingestion of recombinant Lactococcus lactis (L. lactis) was shown to be a valuable alternative. Starting thereof we have developed a novel pharmaceutical platform. Our expertise and TopAct (topical and active) delivery technology allows use of recombinant L. lactis- ActoBiotics- in clinical practice. Here we discuss the development of recombinant L. lactis for intestinal delivery of rhIL-10 in humans.