Cellular signals for the induction of human interleukin-1 receptor antagonist

The polypeptide cytokine interleukin-1 (IL-1) mediates a broad spectrum of inflammatory, metabolic, physiologic, hematopoietic, and immunologic properties. An inhibitor of IL-1 (IL-1ra) has been purified from monocytes, and its DNA has been cloned. Human immunoglobulin G stimulates monocytes to make IL-1ra, but the monocyte receptor(s) for this induction remains a mystery. Therefore, the cellular Fc receptors (Fc gamma R) for IgG that induce IL-1ra production were tested. The Fc gamma R were defined and quantitated by flow cytometer. Anti-Fc gamma RIII (CD16), anti-Fc gamma RII (CD32), and anti-Fc gamma RI (CD64) had no blocking effect on IL-1ra production from monocytes after IgG stimulation. Monocytes express Fc gamma RI and II and respond as anti-CD32 to secrete IL-1ra; neutrophils express Fc gamma RII and III and respond as anti-CD16 to secrete IL-1ra; macrophages express Fc gamma RI, II, and III and respond as both anti-CD16 and anti-CD32 to secrete IL-1ra. These studies strongly suggested that both Fc gamma receptor II and III play a key role in IL-1ra production.