Modulation of Immunological Histamine Release from Human Lung Fragments by Stem Cell Factor, Il-3, Il-5 and Gm-Csf: Comparison with Human Leukocytes

Because of the importance of cytokines in the regulation of allergic inflammation, we investigated the effects of SCF, IL-3, IL-5 and GM-CSF on immunological histamine release from sensitized human lung fragments as well as human leukocytes. SCF (0.2-20 ng/ml) caused a concentration-related enhancement of anti-IgE (1/100) induced histamine release from lung fragments reaching maximally 64% at 20 ng/ml. In contrast, enhancement produced by IL-5, IL-3 and GM-CSF (0.2-20 ng/ml) was quite marginal and reached at best around 20% at the higher concentration, IL-5 being slightly more effective than IL-3 and GM-CSF. Further, SCF potentiated histamine release whatever the level of immunological control whereas potentiation by IL-5 primarily occurred when the amount of histamine release induced by the immunological control ranged between 5 and 10%. SCF acted synergistically with IL-5, producing a greater enhancement of histamine release than the sum of each cytokine used alone. Both SCF and, to a lesser extent, IL-5 potentiated anti-IgE-mediated histamine release regardless of passive sensitization of lung fragments. Unlike what was observed with lung fragments, IL-3, GM-CSF and to a lesser extent IL-5, were potent enhancing agents of anti-IgE (1/2,000)-induced histamine release from leukocytes. Maximal enhancement produced by IL-3 (20 ng/ml), GM-CSF (2 ng/ml) and IL-5 (20 ng/ml) reached 92%, 78% and 61%, respectively. By contrast, SCF (0.2-20 ng/ml) was ineffective on human leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS