INHIBITION OF STEM-CELL FACTOR-DEPENDENT FORMATION OF HUMAN MAST-CELLS BY INTERLEUKIN-3 AND INTERLEUKIN-4

In murines, interleukins (IL) 3, 4, 9, and 10, nerve growth factor, an d stem cell factor induce or promote growth and differentiation of mas t cells (MC). Increased stimulation and synergy was observed when comb inations of-cytokines were used. In man, no growth factor for human MC s had been identified until recently, when SCF was found to induce in vitro growth and differentiation of human MCs. In the present study, t he effects of recombinant human IL-3 and IL-4 on SCF-dependent differe ntiation of human MCs from their circulating progenitor cells in long- term culture were analyzed. Surprisingly, both IL-3 and IL-4 were foun d to inhibit SCF-dependent formation of human MCs (SCF, 100 ng/ml: 36. 4+/-18.7x10(3)/ml; SCF + IL-3, 100 U/ml: 23.4+/-4.2x10(3)/ml; SCF + IL -4, 100 U/ml: 7.4+/-4.4x10(3)/ml) and synthesis of MC tryptase (SCF, 1 00 ng/ml: 73.2+ 17.6 ng/ml; SCF + IL-3, 100 U/ml: 10.8+/-3.1 ng/ml [p< 0.01]; SCF + IL-4, 100 U/ml: 8.1+/-1.5 ng/ml, [p = 0.02]). The inhibit ory effects of these cytokines on SCF-dependent formation of human MCs were associated with an increase in the number of macrophages (IL-3) or lymphocytes (IL-4) in the same cultures and may be due to competiti ve recruitment;of cells from a pool of multilineage hematopoietic prog enitor cells.