Indications and mechanisms of action of the intravenous immunoglobulines in the systemic autoimmune and inflammatory pathologies

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human IgG obtained from pools of more than 1000 healthy blood donors. Initially used for the treatment of immunodeficiencies, IVIg have increasingly been used as immunomodulatory agent in autoimmune and inflammatory disorders. Several mechanisms of action have been described during the last 25 years, including : (i) modulation of Fcgamma receptors expression on leukocytes and endothelial cells ; (ii) interaction with complement proteins ; (iii) modulation of cytokines and chemiokines synthesis and release ; (iv) modulation of cell proliferation and apoptosis ; (v) remyelinisation ; (vi) neutralisation of circulating antibodies ; (vii) selection of immune repertoires and (viii) interaction with other cell-surface molecules on lymphocytes and monocytes. We here discuss the recent advances in the understanding of immunoregulatory effects of IVIg, and we point out the need of new strategies to overcome the predicted increasing worldwide shortage of IVIg.