Neutropenia is a common and often dose limiting side effect of some
chemotherapy regimens. The aim of this study was to investigate the ability of an
immunomodulator, glycosaminylmuramyl
dipeptide (GMDP, CAS 78113-36-7,
romurtide) to reduce
chemotherapy induced
neutropenia. BALB/c mice were treated with 200 mg kg-1
cyclophosphamide (CY) to induce a reversible
neutropenia lasting approximately 6-7 days. There was no change in the duration or depth of
neutropenia in mice treated with GMDP for 3 consecutive days (2.5 or 25 mg kg-1) starting the day after CY injection. In addition, at the doses used, the time of administration of GMDP relative to CY did not alter this response. However, a marked neutrophilia compared to controls was consistently observed in all cases. Neutrophil counts of up to 14 times the baseline value were measured 6-7 days after the induction of
neutropenia. GMDP had no effect in the absence of CY. Less variation was seen in white cell counts of older non-SPF mice treated with CY. When the activity of GMDP (5 mg kg-1) was compared with
G-CSF (
granulocyte colony stimulating factor, 100 micrograms kg-1) in these animals, GMDP showed a consistent trend to reduce the length of
neutropenia, however, under the conditions tested only
G-CSF treatment resulted in a significant reduction in the duration of
neutropenia. In the 12-week-old mice, the neutrophilia seen with both
G-CSF and GMDP was much smaller than in the 8-week-old mice, and was not significantly different from that in control mice treated with CY alone.