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‐1α, IL‐1β, tumor necrosis factor‐α 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.