Stimulatory effect of romurtide on hematopoiesis in monkeys

Repeated subcutaneous injections of romurtide (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18), muroctasin; CAS 78113-36-7), a synthetic muramyl dipeptide derivative, increased significantly the number of peripheral neutrophils and monocytes in a dose-dependent fashion in healthy cynomolgus monkeys (Macaca fascicularis). The number of platelets was also increased significantly in monkeys with repeated dosing of romurtide. After single dosing of romurtide (1 mg/head), neutrophils counts showed a marked increase within 24 h and at 120 h after romurtide injection. Monocytes counts were decreased transiently until 8 h, but were increased persistently from 48 to 120 h after injection. Lymphocytes counts were stable throughout the experimental period except for a significant decrease until 24 h. In addition, romurtide stimulated blood neutrophils and monocytes in vivo for enhanced chemiluminescence (CL) responses to opsonized Escherichia coli. When peripheral monocytes from monkeys were incubated with various concentrations of romurtide in vitro, production of colony-stimulating factors (CSFs), interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cells was enhanced significantly, indicating that the augmenting effects of romurtide on the production of various monokines including CSFs by monocytes are involved in the mechanisms of hematopoiesis and enhanced CL generation by phagocytic cells in vivo.