Effects of low dose total body irradiation (LDTBI) and recombinant human interleukin-2 in mice.

Abstract

10-16-Week-old female BALB/c mice received low dose total body irradiation (LDTBI) in one fraction immediately before the beginning of treatment with recombinant human interleukin-2 (rIL-2). LDTBI prevented in a dose-dependent manner the weight increase of the spleen, liver and lungs induced by fluid extravasation provoked by rIL-2 injections. It also limited the increase of the number of mononuclear cells in the spleen induced after in vivo treatment with rIL-2. Immunofluorescence analysis of spleen cells revealed that LDTBI decreased the relative sIgM+ cell number in spleen, while the relative numbers of Lyt-1+, Thy-1+ and L3T4+ cells were increased, indicating that a T and/or NK population, radioresistant to LDTBI, could still proliferate under rIL-2 stimulation in vivo. Such lymphocytes were capable of in vitro lysis of YAC cells in a 4-hour 51Cr release assay, as well as lymphokine-activated killer (LAK) cells obtained in mice treated with rIL-2 alone. Thus, LDTBI given prior to rIL-2, yet preserving the cytotoxic capacity of the LAK cells activated by rIL-2, could prevent the vascular leak syndrome toxicity induced by rIL-2 injection.