Protective effect of ren-shen-yang-rong-tang (Ninjin-Youei-to) in mice with drug-induced leukopenia against Pseudomonas aeruginosa infection

When 200 mg/kg of cyclophosphamide (CY) or 5-fluorouracil (5-FU) were given subcutaneously to mice, severe reduction of leukocyte numbers in the peripheral blood was observed on day 4 and from day 4 to day 8 after the treatment, respectively. Daily administration of ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT), (1 g/kg/day) and recombinant human granulocyte-colony stimulating factor (rhuG-CSF, 2, μg/mouse/day) either from day 0 to day 4 after treatment with CY or from day 0 to day 8 after treatment with 5-FU accelerated the recovery of peripheral leukocytes. Administration of NYT and rhuG-CSF inhibited deceases in the number of colony forming units in the spleen (CFU-S) in drug-treated mice. In mice infected intraperitoneally with a virulent strain of Pseudomonas aeruginosa 4 days and 8 days after treatment with CY and 5-FU, respectively, lethal doses were much lower (approximately 1/1000) than that in normal mice. Administration of NYT and rhuG-CSF to drug-treated mice inhibited the enhanced bacterial growth in the peritoneal cavity. Administration of NYT or rhuG-CSF to drug-treated mice enhanced the recovery of accumulation of leukocytes into the infected peritoneal cavity from their depressed state. Administration of NYT was more effective for improving the host resistance of 5-FU-treated mice than for improving that of CY-treated mice in contrast to rhuG-CSF which exhibited stronger effect in CY-treated mice than in 5-FU treated mice.