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.
Banning
Ursula
U
Department of Pediatric Hematology, Oncology and Hemostaseology, Clinic for Children and Adolescents, University of Leipzig Medical Center, Leipzig, Germany. Ursula.Banning@medizin.uni-leipzig.de
Krutmann
Jean
J
Körholz
Dieter
D
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D045743:Scleroderma, Diffuse / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
D024042:Collagen Type I; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma