RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR ACCELERATES REGENERATION AFTER T-2 TOXIN-INDUCED HEMOPOIETIC INJURY AND LESSENS LETHALITY IN MICE

The effects of rhG-CSF on T-2-induced leukopenia and lethal toxicity in mice were investigated. First, T-2 was administered by gavage to adult male mice at a dose of 3 mg/kg b. w. daily for 7 days, and rhG-CSF was given i. p. in daily dose of 10 or 30 μg/kg b. w./day, beginning on the 2nd day, for 5 days. The peripheral WBC of mice receiving T-2 alone was decreased to one fourth of control counts, and bone marrow (BM) cell counts were also markedly diminished. The administration of rhG-CSF prevented those T-2-induced depressions. Histologically, the delation of the hematopoietic cells from BM and spleen of mice given T-2 was remarkably counteracted by administration of rhG-CSF. In the other experiment, rhG-CSF was injected i. p. for 5 days beginning on the next day of the 7-day T-2 administration. The recovery of WBC and BM cell counts was hastened by rhG-CSF reaching the control level in 6 days, and differential leukocyte analysis revealed an increase of neutrophils. Furthermore, simultaneous administration of rhG-CSF depressed the T-2-induced lethal toxicity, dose-dependently. The results revealed that rhG-CSF possesses a potent ability to protect T-2-induced leukopenia and lethality in mice, and it could be used as an antidote against T-2 and related trichothecene-induced acute intoxication.