Inhibition of human mast cell growth and differentiation by interferon gamma-1b

In an effort to identify cytokines that inhibit human mast cell growth, we cultured HMC-1 cells and recombinant human stem cell factor (rhSCF)- dependent human bone marrow-derived mast cells (HBMCs) in the presence of interferon gamma (IFNγ)-1b and interferon alpha (IFNα)-2b. HMC-1 cell numbers decreased in the presence of 1000 U/mL IFNγ-1b but were unaffected by 1000 U/mL of IFNα-2b. HBMCs were then cultured for 0 to 7 days with 100 ng/mL rhSCF and 10 ng/mL recombinant human IL-3 (rhIL-3), followed by culture in rhSCF and administration of either 1000 U/mL IFNα-2b or 1000 U/mL IFNγ-1b. HBMCs appearing in cultures with rhSCF alone or in combination with IFNα-2b were virtually identical in number through 8 weeks of culture. In cultures supplemented with IFNγ-1b, HBMCs significantly decreased in number and incidence of granular metachromasia by 4 to 5 weeks (p < 0.001). Similar results were obtained when human marrow was cultured from day 0 with rhSCF and IFNγ-1b. Mature rhSCF-dependent HBMCs were also cultured at 5 weeks with rhSCF alone or in combination with IFNγ-1b. Compared with cells cultured in rhSCF, mature 5-week HBMC cultures treated with rhSCF plus IFNγ-1b revealed a decrease in mast cells, and those mast cells that remained had fewer toluidine blue- and tryptase-positive granules after 5 to 8 weeks. FACS analysis of rhSCF plus IFNγ-1b-treated mature HBMCs revealed increased c-kit and Fc(ε)RI expression. Mast cell releasibility was not increased. IFNγ-1b was thus able to suppress mast cell growth from CD34⁺ cells, suggesting that this agent should be considered as a candidate cytokine for the treatment of disorders of mast cell proliferation.