ROMURTIDE, A SYNTHETIC MURAMYL DIPEPTIDE DERIVATIVE, PROMOTES MEGAKARYOCYTOPOIESIS THROUGH STIMULATION OF CYTOKINE PRODUCTION IN NONHUMAN-PRIMATES WITH MYELOSUPPRESSION

The response of megakaryocytes and cytokines to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in monkeys with myelosuppression by carboplatin-treatment. Romurtide i ncreased the number of megakaryocytes and promoted the shift of megaka ryocytes towards high ploidy class indicative of the promotion of the proliferation and maturation of megakaryocytes. The serum levels of in terleukin-6, stem cell factor, and erythropoietin elevated significant ly before the enhanced response of megakaryocytes induced by romurtide was observed. Romurtide also enhanced production of colony-stimulatin g factors (CSFs), such as granulocyte-CSF, macrophage-CSF, and granulo cyte-macrophage CSF by monkey mononuclear cells. The stimulating effec t of romurtide on the production of those cytokines and CSFs is likely to be responsible for the subsequent promotion of the proliferation a nd maturation of marrow megakaryocytes. (C) 1997 Elsevier Science Ltd.