Histamine-releasing lymphokine--characteristics of its production

The in vitro production of the histamine-releasing lymphokine (histamine-releasing factor, HRF) was studied. HRF was found to be producible from the mononuclear cells of most individuals following stimulation with the T-cell mitogen-concanavalin-A (Con-A). Kinetic studies showed that HRF production was an early event in cellular response to activation--beginning as early as 6 h after activation thus preceding lymphoproliferation which was not apparent until about 24 h after activation. Only a 3 h pulse-stimulation of the cells was found to be necessary for HRF production to occur. Furthermore, the presence of foetal calf serum supplement in the culture medium was found to be unimportant for production. Inhibitors of DNA, RNA and protein synthesis--mitomycin C, actinomycin D and puromycin respectively, in a dose range of 10-25 micrograms/ml, completely abolished HRF production. The results are discussed with regards to the nature of HRF as a genuine product of lymphocyte activation.