IgG induction of IL-1 receptor antagonist production by human monocytes.

In summary, IL-1ra is a unique cytokine that binds avidly to cell surface receptors for IL-1 without inducing any detectable intracellular responses. Adherent IgG and LPS induce IL-1ra production in human monocytes through different mechanisms. IL-1ra has been shown to be an effective competitive inhibitor of IL-1 both in vitro and in vivo (Arend 1993). The possibility exists that stimulation or enhancement of endogenous IL-1ra production may be an efficacious therapeutic approach in human diseases where local IL-1 may play an important role in pathophysiology. Our studies have demonstrated that IL-1ra production is induced in human monocytes in vitro by either culture on adherent IgG or culture with i.v.Ig preparations. Our initial studies failed to show increased IL-1ra levels in the peripheral circulation of patients with Kawasaki's Disease after i.v.Ig administration. However, our preliminary approaches may not have been sufficiently complete and a more extensive examination of the effects of i.v.Ig on IL-1ra production in vivo is warranted.