Human, recombinant interleukin-2 induces in vitro histamine release in a dose-dependent manner

We previously observed that human, recombinant interleukin-2 in a pharmacologic dose (200 u/ml) induced histamine release from monocyte-depleted peripheral blood mononuclear cells in vitro. Therefore, we studied the role of various pharmacologic doses of rIL-2 on in vitro histamine release. Peripheral blood mononuclear cells (5 x 10(6) cells/ml), which also contain basophils, from 13 patients scheduled for elective colorectal cancer surgery and 10 age and sex matched healthy volunteers were stimulated with rIL-2 in concentrations of 0, 50, 100, 200, 450, 900, 1,800 and 3,600 u/ml, respectively, for 1, 24 and 48 hours under standard conditions. Histamine was analysed in supernatants using the glass fiber method. Simultaneously, total cell-bound histamine was analysed in lysate from 5 x 10(6) mononuclear cells from all patients and volunteers, thus allowing determination of percent histamine release. Supernatant histamine concentration from unstimulated cells was 17.2 +/- 1.5 ng/ml in patients compared to 7.9 +/- 1.0 ng/ml in volunteers (#p < 0.05) after 1 hour stimulation, and no further increase was observed after 24 and 48 hours, respectively. Histamine concentration increased significantly in the supernatant from cells stimulated by rIL-2 in a dose-dependent manner both in patients and volunteers. Total cell-bound histamine was 49.3 +/- 4.1 ng/ml in patients compared to 78.5 +/- 7.7 ng/ml in volunteers (p < 0.05). Therefore, both spontaneous and rIL-2-induced histamine release was significantly enhanced in cancer patients compared to volunteers (*p < 0.05). These data suggest that rIL-2 in high pharmacologic doses stimulates in vitro histamine release in a dose-dependent manner in both cancer patients and volunteers. This may in part explain the severe toxicity observed during high-dose rIL-2 therapy.