IL-4 RELEASE BY HUMAN LEUKEMIC AND ACTIVATED NORMAL BASOPHILS

Recently, authors have addressed the ability of human basophils to pro duce IL-4. We report here the detection of significant serum IL-4 leve ls in a case of acute transformation of chronic myelogenous leukemia w ith a predominant basophilic cell population. Leukemic basophils were isolated from patients' PBMC and assayed for their IL-4-mRNA expressio n and their ability to secrete this cytokine in vitro. Leukemic basoph ilic cells (>90% toluidine blue positive) but not other PBMC expressed IL-4-mRNA, contained IL-4 protein, and secreted this cytokine. These cells had a spontaneous IL-4 secretion ability, without a need for an exogenous activator. Meanwhile, while, IL-4 release was significantly increased following leukemic cell activation through FcepsilonRI-ligat ion or by Ca2+ ionophore. IL-4 and its mRNA were also detected in leuk emic basophils from three other chronic myelogenous leukemia patients with moderate basophilia (13, 14, and 23% basophils in PBMC). To confi rm these data in normal human cells, we have developed a method to obt ain large numbers of purified basophils from human bone marrow cell cu ltures. In contrast to leukemic basophils, normal cells required in vi tro activation through FcepsilonRI ligation or by Ca2+ ionophore to ex press and secrete IL-4. Leukemic and normal basophils secreted histami ne following in vitro activation, but were negative for tryptase. Thes e data thus demonstrate the in vivo and in vitro ability of human baso phils to produce IL-4.