Increased In Vivo Antibody Activity Against Interferon α, Interleukin-1α, and Interleukin-6 After High-Dose Ig Therapy

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AbstractHigh-avidity antibodies against interferon α (IFNα), interleukin-1α (IL-1α), and IL-6 have been demonstrated in preparations of normal human IgG, and in vivo modulation of these cytokines may therefore account for immunomodulatory and anti-inflammatory effects of high-dose intravenous IgG therapy. We have investigated the in vivo recovery and the effect on serum cytokine levels of antibodies to IFNα, IL-1α, and IL-6 infused with IgG preparations. Fifteen treatment series of 0.4 g IgG/kg/d were administered over 3 days to eight patients with autoimmune diseases. All IgG preparations contained variable amounts of antibodies binding to 125I-labeled human IFNα2A, -IL-1α, and -IL-6, and the contents of these molecules correlated with increased levels in serum anticytokine activities after IgG infusion. The infused anti–IL-1α antibody activity was fully recovered, whereas the recovery of anti-IFNα2A antibodies was significantly reduced. Serum antiviral activities were significantly reduced after IgG therapy (before, 0 to 5.6 IU/mL; after, 0 to 0.6 IU/mL). In contrast, enzyme-linked immunosorbent assay (ELISA) showed no significant reduction in the serum levels of IL-6 (before, 1 to 70 pg/mL; after, 2 to 55 pg/mL), and the levels of IL-1α were consistently below the detection limit (<30 pg/mL). In conclusion, increased levels of antibodies to IFNα2A, IL-1α, and IL-6 occurred in patients receiving IgG and this reduced the serum antiviral activity.