Normalization of peripheral blood cell composition by lactoferrin in cyclophosphamide-treated mice

Cyclophosphamide (CP) is used in the treatment of autoimmune disorders and leukemia. The compound induces severe leuko- and neutropenia. Lactoferrin (LF) is a protein which plays a role in the innate immunity. In this study we evaluated the usefulness of LF in reversing CP-induced lympho- and neutropenia in mice. CBA mice were treated with CP (350 mg/kg body weight, intraperitoneally) and given LF as a 0.5% addition to drinking water. Alternatively, LF was administered orally (seven doses, 1 mg each) on alternate days following CP injection. Control groups received CP or LF only. Blood samples were taken before treatment and on days 4, 8, 15 and 22 following CP injection to determine leukocytosis and cell types in blood smears. Mice treated with CP showed severe leukopenia, strong eosinophilia (day 4), and an altered lymphocyte/neutrophil ratio (days 8-22). Treatment of mice with LF for 21 days partially normalized the cell composition in CP-treated mice (increased percentage of lymphocytes and decreased eosinophil content). The content of leukocytes increased upon LF treatment on days 4, 8, 15 and 22 (by 36.8, 39.5, 72 and 70.7%, respectively). More importantly, LF partly normalized the neutrophil and lymphocyte composition on day 22 (neutrophils: 29.2% in control mice, 50.6% in CP-treated, and 39.16% in CP/LF-treated; lymphocytes: 66.18% in control mice, 35% in CP-treated and 48.8% in CP/LF-treated). Administration of LF alone did not change the cell numbers or composition. LF given orally to CP-immunocompromised mice accelerates reconstitution of lymphopoiesis and myleopoiesis.