Study on the reduction of chemotherapy induced neutropenia in mice using glucosaminylmuramyl dipeptide.

Abstract

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.

• Authors: N A Armstrong, E J Bolton, D L Morris
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 49 Issue 8 Pg. 716-20 (Aug 1999) ISSN: 0004-4172 [Print] Germany
• PMID: 10483520 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antineoplastic Agents, Alkylating
• Acetylmuramyl-Alanyl-Isoglutamine
• glucosaminylmuramyl-2-alanine-D-isoglutamine
• Granulocyte-Macrophage Colony-Stimulating Factor
• Cyclophosphamide

Topics

• Acetylmuramyl-Alanyl-Isoglutamine (analogs & derivatives, therapeutic use)
• Adjuvants, Immunologic (therapeutic use)
• Animals
• Antineoplastic Agents, Alkylating
• Behavior, Animal (drug effects)
• Cyclophosphamide
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• Leukocyte Count (drug effects)
• Mice
• Mice, Inbred BALB C
• Neutropenia (chemically induced, drug therapy)