Cytokines for the treatment of thrombocytopenia

Multiple cytokines affect the cellular processes that occur during the transition of a hematopoietic stem cell (HSC) to a platelet. Thrombopoietin (TPO) is the physiological regulator of thrombopoiesis. Although a number of cytokines (interleukin [IL]-1, IL-3, and IL-6) were first evaluated for their ability to lessen the degree of thrombocytopenia occurring during a variety of clinical scenarios, their clinical development was abandoned due to their limited effectiveness or excessive toxicity. Clinical results with TPO and a truncated pegylated form of TPO, megakaryocyte growth and development factor (MGDF), were more promising, but the repeated use of MGDF resulted in the development of neutralizing antibodies. This adverse event halted the further clinical development of not only MGDF but also TPO. IL-11 also affects various stages of megakaryocytopoiesis and thrombopoiesis and its use has been shown to shorten the duration of chemotherapy-induced thrombocytopenia, which led to its approval by the US Food and Drug Administration (FDA). A growing number of new non-immunogenic peptides and non-peptide TPO agonists recently have entered clinical trials. These small molecules appear to be effective therapies and have acceptable toxicity, but additional clinical evaluation will be required prior to their approval for clinical use. © 2007 Elsevier Inc. All rights reserved.