IL-15 SA treatment causes systemic toxicity and the study of kinetics of IL-15 SA toxicity. (A) In dose escalation studies, WT C57BL/6 mice received i.p. injection of 0, 0.5, 1, and 2 μg IL-15 SA for 4 consecutive days (days 0–3). Body temperature and mortality were recorded daily on days 0–4. (B) To assess the temporal effect of IL-15 SA, WT mice received daily administration of 2 μg IL-15 SA for 4 d. Untreated WT mice served as control. Body weight was measured daily from days 0 to 4. Values represent body weight changes compared with the initial day 0 measurements. (C) Serum AST and ALT concentrations were measured at 24 h after the fourth i.p. injection of 2 μg IL-15 SA. Vehicle-treated mice served as control. (D) Upon 4 d of 2 μg IL-15 SA treatment, spleens were harvested from WT mice. Untreated WT mice were included as control. Spleen weights were measured in the two groups. (E) To study the kinetics of IL-15 SA toxicity, WT mice were treated with 2 μg IL-15 SA treatment for 4 d. Body temperature was measured at 24 and 48 h as well as 1, 2, 3, 4, and 7 wk after the last treatment of IL-15 SA. n = 8–10 mice/group. Data are representative of two to four separate experiments. *p < 0.05 compared with designated control.