Generation of the Complement Activation Product C5a Precedes Interleukin-2-Induced Capillary Leakage Syndrome

Capillary leakage syndrome (CLS) is a severe side effect of intravenous interleukin-2 (IL-2) therapy. Twenty-seven cycles of IL-2 therapy [six (day 1), nine (day 2), and 12 × 10⁶ U/m² body surface (days 3 to 5), given as continuous infusion] were analyzed in children and adolescents. The anaphylatoxin C5a was assessed as an early predictor for CLS. CLS developed in 11 of 27 cycles of IL-2 infusion. C5a at day 2 of IL-2 infusion (0.80-9.43 μg/L; median, 1.8 μg/L) was increased in CLS patients when compared with baseline values (0.21-0.74 μg/L; median, 0.40 μg/L;p = 0.01) and when compared with C5a at day 2 in non-CLS patients (0.44-1.2 μg/L; median, 0.62 μg/L;p <0.01). Ten of 11 CLS patients showed C5a levels >1.0 μg/L, whereas 14 of 16 patients who did not develop CLS showed C5a <1.0 μg/L (predictive value positive 83% for CLS).