Different behaviour of radioiodinated human recombinant interleukin-1 and its receptor antagonist in an animal model of infection

Recently, we demonstrated that radiolabelled interleukin-l (IL-1) specifically accumulates in focal infection in mice through interaction with its receptor. Unfortunately, systemic side-effects of IL-1 limit its clinical application. We investigated whether this problem could be circumvented by using the interleukin-1 receptor antagonist (IL-Ira), an equally sized protein that binds to the same receptors as IL-1 without induction of biological effects. Biodistribution of¹²⁵I-IL-1 and¹²⁵I-IL-Ira was determined in Swiss mice withStaphylococcus aureus-induced abscesses in the left calf muscle at 4, 12, 24 and 48 h after injection of either 0.4 MBq¹²⁵I-IL1 or 0.4 MBq¹²⁵I-IL-Ira. In vitro, the proteins displayed similar binding characteristics. High-performance liquid chromatographic analysis revealed a tendency for IL-Ira to associate with serum proteins. Both proteins rapidly cleared from most organs. However, the abscess uptake of¹²⁵I-IL-Ira was significantly lower than that of¹²⁵I-IL-1 at all time points (48 h p.i.: 0.06±0.01%ID/g vs 0.60±0.04%ID/g;P<0.02). The abscess-to-contralateral muscle ratios did not exceed 15.5±2.9 for¹²⁵I-IL-lra, while the ratios for¹²⁵I-IL-1 reached 46.9±5.7 at 48 h p.i. Despite similar in vitro receptor binding, the abscess uptake of IL-Ira was much lower than that of IL-1. The interaction of IL-Ira with serum proteins in vivo may reduce its availability for receptor binding in the infection. Although on theoretical grounds IL-Ira is very interesting, these characteristics will prevent its development as a clinically useful radiopharmaceutical to image infection.