Increased resistance to Listeria monocytogenes following subchronic cyclophosphamide exposure: Relationship to altered bone marrow function

Mice administered multiple doses of cyclophosphamide demonstrated a marked resistance to infection with the bacterium, Listeria monocytogenes . In contrast, acute exposure rendered mice more susceptible to infection than untreated controls. Resistance to infection with Listeria , a facultative intracellular organism, is thought to be dependent upon normal antimicrobial activity early after infection and subsequently through generation of primed T cells. Examination of various macrophage and immune functions, however, failed to demonstrate a significant difference between the two cyclophosphamide-treated groups although both groups were immunosuppressed when compared to untreated controls. Adoptive transfer studies into X-irradiated recipients revealed that repopulation with bone marrow cells from subchronic but not acute cyclophosphamide-treated mice, restored resistance. Furthermore, the numbers of granulocyte/macrophage progenitor cells in the bone marrow were elevated in subchronically treated mice but not acute or unexposed controls. These data suggest the selection of a granulocyte/macrophage progenitor cell possessing a high degree of antilisterial activity following subchronic cyclophosphamide treatment. The effects induced by this exposure regimen are probably related to the enrichment of this cell population resulting from the cell cycle stage specific activity of the drug.