Enhancement of platelet recovery in X-irradiated guinea pigs by romurtide,
a synthetic muramyl dipeptide derivative
K Namba, T Otani and Y Osada
Exploratory Research Laboratories 1, Daiichi Pharmaceutical Co, Ltd, Tokyo,
Japan.
The response of megakaryocytes and platelets to the administration of
romurtide, a synthetic muramyl dipeptide derivative, was investigated in
normal and irradiated guinea pigs. Romurtide was administered
subcutaneously in a single dose or daily doses at levels of 1 to 100
micrograms/animal/day to normal animals to assess the dose response.
Subsequently, dosage at 100 micrograms/animal/d for 8 consecutive days was
initiated in separate groups of animals immediately after 1 Gy total body
x-irradiation. In normal animals, a significant dose- dependent increase in
the platelet count was noted, and a prolonged thrombocytopoiesis was
detectable from 7 through 15 days after the initiation of romurtide
administered for 8 days at a dose of 100 micrograms/animal/d. A significant
increase in the white blood cell (WBC) count was also observed during days
1 through 11 after beginning romurtide treatment. In the irradiated
animals, the treatment with romurtide increased platelet counts during the
recovery phase of thrombocytopenia, thus apparently decreasing the time
required for recovery to a normal platelet level. Before the rapid recovery
of platelet counts by romurtide treatment, a marked increase in the number
of megakaryocytes was noted as early as 7 days after irradiation. This
increase was accompanied by an accelerated shift of the size distribution
of megakaryocytes toward larger size class. Thus, the mean megakaryocyte
size was significantly greater in guinea pigs receiving romurtide than in
controls. Preceding the increase in the number of megakaryocytes, the serum
interleukin-6 levels were found to be approximately 5 times greater than
those in control animals. Treatment with romurtide diminished the WBC count
nadir, resulting in significantly higher WBC count levels than in controls.
Elevation of the plasma fibrinogen level was observed in the treated
animals, and normalized gradually after discontinuation of romurtide
treatment. These results indicate a possible therapeutic potential of
romurtide in the management of thrombocytopenia associated with
myelosuppression.
Volume 83,
Issue 9,
pp. 2480-2488,
05/01/1994
Copyright © 1994 by The American Society of Hematology
