Thrombopoietic activity of recombinant human interleukin 11 in cancer patients receiving chemotherapy

Abstract

 Interleukin 11 (IL-11) is a newly identified hematopoietic growth factor that exerts its primary effect on megakaryocyte maturation and platelet production. It has a unique receptor, signaling by which is mediated by the glycoprotein (GP) 130 pathway. IL-11 is synergistic with stem-cell factor (c-kit ligand) in vitro, enhancing proliferation of primitive hematopoietic stem cells, and has been shown to be critical to the process of polyploidization and maturation. In preclinical models, IL-11 was shown to enhance platelet recovery following intensive chemotherapy, and in murine bone-marrow transplant models it accelerates the recovery of all hematopoietic lineages. Nonhuman primate studies have demonstrated a dose-related thrombopoietic effect; however, no myeloid effect has been observed. In clinical phase I trials, subcutaneous IL-11 was well tolerated and induced a dose-related thrombopoietic effect in women with breast cancer. IL-11 at doses of >25 μg/kg per day appeared to reduce the severity of chemotherapy-induced thrombocytopenia. In a randomized phase II trial, IL-11 at 50 μg/kg reduced the requirement for platelet transfusions as compared with that in placebo-treated controls. IL-11 is an interesting factor; however, further studies are needed to confirm its activity and are in progress.