The role of IL-4 and IL-12 in the regulation of collagen synthesis by fibroblasts

Chronic sclerodermifomic graft versus host disease is a rare but important complication of allogeneic hematopoietic stem cell transplantation that especially occurs in patients who are treated with donor lymphocyte infusions for relapse of a malignant disease. Today most knowledge about the pathogenesis of chronic Graft-versus-Host Disease is based on mice models. In this report we describe the development of an allogeneic in vitro model that allows studying the pathogenesis of chronic sclerodermifomic Graft-versus-Host Disease in the human setting. We report that priming of mononuclear cells in the presence of allogeneic fibroblasts and Interleukin (IL)-4 induces fibroblast collagen synthesis, whereas priming in the presence of IL-12 suppresses collagen synthesis during subsequent coculture of primed mononuclear cells with allogeneic fibroblasts. Since IL-12 is also known to mediate anti-tumor effects by stimulation of Natural Killer cell and Lymphokine Activated Killer cell activity, these findings indicate that treatment of patients with IL-12 or pretreatment of donor lymphocytes with IL-12 might strengthen a graft versus leukemia effect and at the same time decrease the risk of chronic sclerodermifomic Graft-versus-Host Disease development.