INTERLEUKIN-4 AND NERVE GROWTH-FACTOR CAN ACT AS COFACTORS FOR INTERLEUKIN-3-INDUCED HISTAMINE PRODUCTION IN HUMAN UMBILICAL-CORD BLOOD-CELLS IN SERUM-FREE CULTURE

In order to better define the role of recombinant interleukins and growth factors in supporting histamine production by histamine-producing-cells (HPC), namely basophils or mast cells, we have conducted experiments in which we compared the abilities of IL-3, IL-4, IL-6 and nerve growth factor (NGF), either alone or in various combinations, to stimulate histamine production from human umbilical cord blood mononuclear cells cultured in either the presence or absence of serum. Over a period of 15 d, IL-3 was able to support intracellular histamine production, in both serum-supplemented and serum-free medium, although the effectiveness of IL-3 was lower in the serum-free cultures. IL-4, NGF and IL-6 taken individually, exhibited little, if any, histamine-promoting activity regardless of whether or not the cells were cultured in serum. Moreover, none of these cytokines significantly enhanced the effect of IL-3 in serum-supplemented cultures. In contrast, IL-3-promoted histamine production in serum-free cultures was significantly enhanced by IL-4 and NGF. These results demonstrate that both IL-4 and NGF can function as cofactors with IL-3 in the support of histamine production in human umbilical cord blood cells.