Effect of preventive administration of lactic acid bacteria on the number and activity of myeloid cells after cyclophosphamide treatment

VILLENA JULIO; SALVA SUSANA; HERRERA MATÍAS; BARBIERI NATALIA; KITAZAWA HARUKI; ALVAREZ SUSANA

Kosice

Simposio; International Scientific Conference on Probiotics and Prebiotics-IPC2010; 2010

European Microbiologists Society

Introduction The daily changes in the number and activity of mature granulocytes and progenitor cells in blood and bone marrow (BM), after an immunosuppression treatment with cyclophosphamide (Cph), were evaluated in mice. In addition, the influence of preventive treatments with lactic acid bacteria (LAB) on the recovery of myeloid cells was studied. Methods@ Swiss-albino mice were fed Lactobacillus casei CRL431 (Lc431, 109 cells/day/mouse) or Lactobacillus rhamnosus CRL1506 (Lr06, 108 cells/day/mouse) for 2 or 5 consecutive days respectively. After each treatment, these groups and untreated controls (CG) received an intraperitoneal (ip) injection of Cph (150 mg/Kg) and were sacrificed at different times post-chemotherapy (for 15d). Total and differential counts, Gr-1 and CD34 expression and peroxidase activity (Px+) of blood and BM cells were studied. Moreover, peritoneal macrophages (PMf) phagocytic activity and Candida albicans (Ca) clearance after an ip challenge were analyzed. Results Cph administration induced a severe leukopenia with neutropenia. Lc431 and Lr06 groups showed a less severe neutropenia and an early recovery of blood neutrophils when compared with CG mice. In BM, Cph decreased the total number of cells affecting both the mitotic and post-mitotic pools. LAB treated groups showed higher numbers of mitotic pool cells and a less severe decrease in the total number of BM cells (P<0.05). Administration of Cph reduced blood and BM Gr-1hi and Gr-1low cells in all experimental groups. However, Lc431 and Lr06 groups showed higher numbers of Gr-1low cells when compared with CG mice during the studied period. Approximately 6% (3.6 106 cells/femur) of nucleated BM cells from untreated mice were committed early and intermediate progenitors (CD34+ cells). Moreover, the majority of CD34+ cells were also Gr-1low positive, which represent immature myeloid progenitors. Both CD34+ and CD34+/Gr-1+ cells in BM were significantly increased by LAB treatments (day 0, before Cph administration). The numbers of BM CD34+ and CD34/Gr-1 cells were reduced by Cph administration in all the experimental groups. However, the reduction of these cells was significantly lower in Lc431 and Lr06 mice. Cph also reduced the number of Px+ cells in blood. Lc431 and Lr06 groups showed a less pronounced decline and earlier recovery of Px+ cells (P<0.05). Mice treated with LAB showed a higher PMf phagocytic activity when compared with CG group (P<0.05). In addition, LAB treatments increased the resistance against Ca challenge, since in these groups, Ca counts in infected tissues were lower than in CG group (P<0.01). Discussion This work demonstrates that LAB treatments are able to increase immature myeloid progenitors in the BM, allowing an early recovery of myeloid cells after Cph administration. LAB are also capable to stimulate phagocytic cells activity. The improvement of both, the number and activity of myeloid cells, is able to increase resistance of immunocompromised mice against infections.