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Development of a Monocyte Activation Test (MAT) to Study Cytokines Induction by IGIV

Thursday, October 11, 2012 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center, Building 45




  • M.C. Anderson
  • E. Marszal
  • B. Abraham
  • D.E. Scott


Immune Globulin, Intravenous (Human) (IGIV), contains IgG purified from thousands of donor plasma units. IGIV infusion is commonly associated with immediate adverse events (AE’s), such as fever, chills, back pain, and nausea. The precise etiology of these events is uncertain, but has been linked in small case studies to increased serum levels of pro-inflammatory cytokines, such as TNF-α. Hypothesized causes of cytokine release include presence of trace amounts of bacterial constituents such as lipopolysaccharide (LPS), and/or intrinsic characteristics of the immune globulin preparations, including aggregated protein. An in vitro monocyte activation protocol to characterize and compare mediator or product induced cytokine profiles was developed. Monocytes were cultured with IGIVs or LPS overnight. An investigational product that was associated with increased rates of infusion-related AE’s consistently increased cell surface IL-15 on a subset of monocytes, while TNF-α and IL-6 were not elevated in culture supernatants. In contrast, LPS stimulation increased production of IL15, TNF-α and IL-6. Similar results were demonstrated using the mouse macrophage cell line, RAW 264.7. Fc receptor (FcR) blockade significantly reduced IL-15 induction by that IGIV lot, suggesting an FcR-mediated mechanism that simulates immune complexes possibly due to protein aggregates. The types of aggregates present will be characterized.

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