185413-30-3

AF12198 competes for binding of ¹²⁵ I-IL-1α with an IC ₅₀ of 8.0 nM, nearly equal to that of IL-1ra, IC ₅₀ of 4.0 nM for the type I receptor.AF12198 (0-5 ng; 8 hours) inhibits IL-6 induction with an IC ₅₀ of 15 μM whereas IL-1ra inhibits with an IC ₅₀ of 2 nM in heparinized human primate blood. Meanwhile, With blood from cynomolgus monkeys, the IC ₅₀ values are 17 μM for AF12198 and 30 nM for IL-1ra. Additionally, AF12198 or IL-1RA alone does not induce IL-6 in blood from either humans or cynomolgus monkeys.

AF12198 (intravenous infusion; 16 mg/kg; 30 min before LPS intravenous injection) significantly attenuates the increase in lung MPO activity induced by LPS in acute lung inflammation and it reduces the lung microvascular leakage from rats inflamed with LPS at the 4 h (32.6%), 12 h (50.1%) and 24 h (65.3%) after LPS.