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Increased In Vivo Antibody Activity Against Interferon  , Interleukin-1, and Interleukin-6 After High-Dose Ig Therapy
Christian Ross,
Morten Svenson,
Henrik Nielsen,
Charlotte Lundsgaard,
Morten Bagge Hansen, and
Klaus Bendtzen
From the Laboratory of Clinical IFN Research and Laboratory of Medical Immunology, Institute for Inflammation Research, Rigshospitalet University Hospital, Copenhagen; Department of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; and Department of Rheumatology, University Hospital Glostrup, Glostrup, Denmark.
High-avidity antibodies against interferon  (IFN), interleukin-1 (IL-1), 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, IL-1, 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 IFN2A, -IL-1, and -IL-6, and the contents of these molecules correlated with increased levels in serum anticytokine activities after IgG infusion. The infused anti-IL-1 antibody activity was fully recovered, whereas the recovery of anti-IFN2A 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-1 were consistently below the detection limit (<30 pg/mL). In conclusion, increased levels of antibodies to IFN2A, IL-1, and IL-6 occurred in patients receiving IgG and this reduced the serum antiviral activity.
Blood, Vol. 90 No. 6 (September 15), 1997:
pp. 2376-2380
© 1997 by The American Society of Hematology.
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