1 research outputs found
Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: More than meets the eye
Intravenous immunoglobulin (IVIg) is a therapeutic preparation of polyspecific human
IgGs purified from plasma pooled from thousands of individuals. When administered
at a high dose, IVIg inhibits inflammation and has proven efficacy in the treatment of
various autoimmune and systemic inflammatory diseases. Importantly, IVIg therapy can
ameliorate both auto-antibody-mediated and T-cell mediated immune pathologies. In
the last few decades, extensive research in murine disease models has resulted in
the elucidation of two novel anti-inflammatory mechanisms-of-action of IVIg: induction
of FcγRIIB expression by sialylated Fc, and stimulation of regulatory T cells. Whereas
controversial findings in mice studies have recently inspired intense scientific debate
regarding the validity of the sialylated Fc-FcγRIIB model, the most fundamental question
is whether these anti-inflammatory mechanisms of IVIg are operational in humans treated
with IVIg. In this review, we examine the evidence for the involvement of these antiinflammatory mechanisms in the therapeutic effects of IVIg in humans. We demonstrate
that although several elements of both immune-modulatory pathways of IVIg are activated
in humans, incorrect extrapolations from mice to men have been made on the molecular
and cellular components involved in these cascades that warrant for critical re-evaluation
of these anti-inflammatory mechanisms of IVIg in humans