Intravenous immunoglobulin (
IVIg)-a preparation of polyclonal serum
IgG pooled from thousands of blood donors-has been used for nearly three decades, and is proving to be an efficient anti-inflammatory and immunomodulatory treatment for a growing number of neurological diseases. Evidence from controlled clinical trials has established
IVIg as a first-line
therapy for
Guillain-Barré syndrome, chronic inflammatory demyelinating
polyneuropathy and multifocal motor neuropathy.
IVIg is also an effective rescue
therapy in some patients with worsening
myasthenia gravis, and is beneficial as a second-line
therapy for
dermatomyositis and
stiff-person syndrome.
IVIg has been tested in some
neurodegenerative disorders, but a controlled study in
Alzheimer disease yielded disappointing results. Despite its widespread use and therapeutic success, the mechanisms of action of
IVIg are poorly understood. Several hypotheses, based on the function of either the variable or constant
IgG fragments, have been proposed to explain
IVIg's immunomodulatory activity. This Review highlights emerging data on the mechanisms of action of
IVIg related to its anti-inflammatory activity, especially that involving the cellular Fcγ receptors and Fc glycosylation. We also summarize recent trials in neurological diseases, discuss potential
biomarkers of efficacy, offer practical guidelines on administration, and provide a rationale for experimental trials in
neuroinflammatory disorders.