Increased in vivo antibody activity against interferon alpha, interleukin-1alpha, and interleukin-6 after high-dose Ig therapy.

High-avidity antibodies against interferon alpha (IFN alpha), interleukin-1alpha (IL-1alpha), 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 IFN alpha, IL-1alpha, 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 IFN alpha2A, -IL-1alpha, and -IL-6, and the contents of these molecules correlated with increased levels in serum anticytokine activities after IgG infusion. The infused anti-IL-1alpha antibody activity was fully recovered, whereas the recovery of anti-IFN alpha2A 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-1alpha were consistently below the detection limit (<30 pg/mL). In conclusion, increased levels of antibodies to IFN alpha2A, IL-1alpha, and IL-6 occurred in patients receiving IgG and this reduced the serum antiviral activity.