Study on the reduction of chemotherapy induced neutropenia in mice using glucosaminylmuramyl dipeptide.
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.
Armstrong
N A
NA
University of New South Wales, Department of Surgery, St. George Hospital, Sydney, Australia.
Bolton
E J
EJ
Morris
D L
DL
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D001522:Behavior, Animal / Q000187:drug effects; D003520:Cyclophosphamide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000139:chemically induced* / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D018906:Antineoplastic Agents, Alkylating; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide