SERUM GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) AND INTERLEUKIN-1(IL-1) CONCENTRATIONS AFTER CHEMOTHERAPY-INDUCED NEUTROPENIA IN NORMAL AND TUMOR-BEARING DOGS

Hematopoiesis is regulated by complex interactions of hematopoietic gr owth factors known as colony-stimulating factors and interleukins. We used sensitive bioassays to quantitate serum granylocyte colony-stimul ating factor (G-CSF) and interleukin-1 (IL-1) concentrations in normal and tumor-bearing dogs following administration of myelosuppressive c hemotherapy (vincristine, doxorubicin, cyclophosphamide). Serum G-CSF and IL-1 increased during the neutrophil nadir in 13 of the 16 dogs. S erum G-CSF concentrations were significantly increased in normal and i n tumor-bearing dogs on neutropenic compared to non-neutropenic days. Serum IL-1 concentrations increased significantly on neutropenic days in normal dogs but not in tumor-bearing dogs. A marked neutrophilia wa s observed in normal dogs, but not in tumor-bearing dogs, following th e increases in serum G-CSF and IL-1 concentrations (days 7, 8, and 9, p < 0.05). Normal dogs produced significantly more G-CSF on neutropeni c days compared to dogs with lymphoma. On non-neutropenic days, serum IL-1 concentrations were significantly increased in dogs with lymphoma and in dogs with nonlymphoid malignancies compared to normal dogs. Th ese results suggest an important role for G-CSF and IL-1 in hematopoie tic recovery after chemotherapy-induced myelosuppression and document an altered hematopoietic regulation in animals with malignancy compare d to normal subjects.