PRECLINICAL BIOLOGY OF INTERLEUKIN-11 - A MULTIFUNCTIONAL HEMATOPOIETIC CYTOKINE WITH POTENT THROMBOPOIETIC ACTIVITY

Interleukin 11 (IL-11) is a multifunctional hematopoietic cytokine which was originally identified as a factor produced by an IL-1-stimulated primate stromal cell line. The in vitro biological activities of recombinant human (rHu)IL-11 result predominantly from synergistic interactions with other growth factors. In combination with other cytokines, rHuIL-11 has been shown to support the formation of primitive hematopoietic and lymphohematopoietic progenitor colonies from bone marrow, to promote erythroid burst formation and to stimulate both early and late stages of megakaryocyte proliferation and differentiation. rHuIL-11 is biologically active in mice, rats, dogs and primates when administered as a single agent in vivo. The predominant effect of rHuIL-11 in naive mice was on cells of the megakaryocytic lineage, increasing the number of bone marrow megakaryocyte progenitors, stimulating megakaryocyte endoreplication and increasing peripheral platelet counts in a dose-dependent fashion. Similar megakaryocytic stimulatory activity was seen in nonhuman primates treated with rHuIL-11 where platelet counts were increased by as much as 300%. In several models of severe myelosuppression induced by chemotherapy and/or irradiation and in bone marrow transplant models, there were multilineage hematopoietic stimulation following rHuIL-11 treatment, In these models, accelerated recovery of platelets was a consistent observation, while some models show enhanced neutrophil and red blood cell recovery as well. These results from preclinical studies confirm the broad spectrum of biological activities exhibited by rHuIL-11 in vitro, and suggest that this cytokine may be an effective agent in the treatment of myelosuppression and thrombocytopenia associated with cancer chemotherapy and bone marrow transplantation.