Alterations in lymphokine secretion during leukemogenesis

The production of interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 3 (IL-3) and granulocyte/macrophage colony stimulating factor (G/M-CSF) by preleukemic and leukemic spleen cells from Balb/c mice infected with Moloney leukemia virus (MoLV) was examined. During the development of the leukemia, the secretion of IL-1 and IL-2 significantly decreased, while the secretion of IL-3 and G/M CSF was not affected and was even enhanced. In addition, a 10 fold increase in the number of colony forming units in cultures (CFU-C) was found in the leukemic spleen indicating a shift in hematopoiesis from the bone marrow (BM) to the spleen. The low levels of IL-2 found in the conditioned medium of Concanavalin A (Con A) activated leukemic spleen cells could not result from active consumption of IL-2 by the cells, pointing to a genuine defect in IL-2 production. This failure of IL-2 secretion could be partially overcome by the addition of phorbol 12 beta-myristate 13 alpha-acetate (PMA) to the cells but not by the addition of IL-1. The defect in IL-2 production and the enhancement in IL-3 and G/M-CSF production may be of significance in the progression of preleukemic cells to autonomous malignant cells.