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, and stem cell factor induce or promote growth and differentiation of mast cells (MC). Increased stimulation and synergy was observed when combinations of cytokines were used. In man, no growth factor for human MCs had been identified until recently, when SCF was found to induce in vitro growth and differentiation of human MCs. In the present study, the effects of recombinant human IL-3 and IL-4 on SCF-dependent differentiation of human MCs from their circulating progenitor cells in long-term culture were analyzed. Surprisingly, both IL-3 and IL-4 were found to inhibit SCF-dependent formation of human MCs (SCF, 100 ng/ml: 36.4 +/- 18.7 x 10(3)/ml; SCF + IL-3, 100 U/ml: 23.4 +/- 4.2 x 10(3)/ml; SCF + IL-4, 100 U/ml: 7.4 +/- 4.4 x 10(3)/ml) and synthesis of MC tryptase (SCF, 100 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 inhibitory 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 competitive recruitment of cells from a pool of multilineage hematopoietic progenitor cells.