SELECTIVE INDUCTION OF INTERLEUKIN-1 RECEPTOR ANTAGONIST AND INTERLEUKIN-8 IN HUMAN MONOCYTES BY NORMAL POLYSPECIFIC IGG (INTRAVENOUS IMMUNOGLOBULIN)

We have investigated the effects of Intravenous immunoglobulin (IVIg), a therapeutic preparation of normal human polyspecific IgG, on the synthesis and release of cytokines by peripheral blood monocytes. IVIg was found to selectively induce gene transcription and secretion of interleukin-1 receptor antagonist (IL-1ra) and IL-8 in cultures of normal human monocytes. The addition of IVIg to cultures of purified monocytes induced a dose-dependent secretion of IL-1ra and IL-8 without stimulating the production of IL-1 alpha, IL-1 beta, tumor necrosis factor-a or IL-6. The effects of IVIg required both the Fc and F(ab ')(2) portions of IgG. IVIg-induced production of IL-8 by monocytes was enhanced by lipopolysaccharide (LPS), although LPS inhibited the secretion of IL-1ra, suggesting that IVIg and LPS stimulate distinct intracellular pathways in monocytes. Induction of IL-1ra and IL-8 by IVIg was enhanced in the presence of autologous T lymphocytes. Our observations document the selectivity of the effects of IVIg on the synthesis of cytokines and cytokine antagonists by human monocytes. Induction of IL-1ra and IL-8 by IVIg may contribute to the anti-inflammatory effects of immunoglobulin therapy in patients with autoimmune and systemic inflammatory disorders.