Present and future clinical relevance of interleukin 3

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Abstract
Interleukin 3 (IL‐3) is a hematopoietic growth factor with a pronounced thrombopoietic activity as well as a broad spectrum of activities on multipotent, committed and mature cells of different lineages. Available for clinical trials since 1989, IL‐3 has been used in well over two thousand patients. In numerous phase I‐II clinical trials, the tolerability profile and the various biologic activities have been defined, and ongoing phase III trials will finally establish its clinical relevance. Doses between 2.5 and 10 μg/kg/d given subcutaneously are well tolerated, cause low grade fever, occasional flu‐like symptoms and headache. At these doses IL‐3 enhances platelet and neutrophil recovery after cycles of myelotoxic chemotherapy, resulting in better adherence to the planned chemotherapy doses and schedules and a decrease in the need for platelet transfusions. Accelerated engraftment of platelets and neutrophils is seen with IL‐3 also after bone marrow transplantation. The effect on neutrophil recovery can be enhanced by the use of a myeloid growth factor such as granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or granulocyte (G)‐CSF after five to 10 days of IL‐3. Treatment enhancement is related to the effect of IL‐3 on the proliferation of hematopoietic progenitors, which leads to an increase in target cells for GM‐ or G‐CSF. Because of the increase in bone marrow proliferation, IL‐3 is being used to increase the mobilization of progenitor cells to the blood and in bone marrow failure. All data derived from phase 1‐11 studies so far indicate that IL‐3 alone or in combination with other cytokines is likely to become the first thrombopoietic factor available for clinical use and that it will allow cancer patients to receive standard chemotherapy at the scheduled intervals and planned doses and to intensify treatment where a higher dose is expected to lead to increased cure rates.

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