Facing the Enigma of Immunomodulatory Effects of Intravenous Immunoglobulin

Abstract

Intravenous immunoglobulin (IVIg) is a safe remedy for a number of conditions; it is produced from human plasma of thousands of healthy donors. The therapeutic effect of IVIg lies within its content. IVIg contains natural antibodies, which are more polyreactive than immune antibodies, including immunoglobulin G antibodies against endogenous and exogenous antibodies, immunomodulating peptides, and varies cytokines. Beneficial effects of IVIg have been established in immunodeficiencies, as well as in some autoimmune diseases. Also, numerous therapeutic effects of IVIg have been reported over the years in varies autoimmune diseases, recurrent pregnancy loss, and cancer. Many proposed immunoregulatory mechanisms of action of IVIg have been suggested. Some of them have been proven, others are still an enigma, at least in part. Some of these mechanisms entail (a) Fc-receptor blockade; (b) neutralization of pathogenic autoantibodies via idiotypic and anti-idiotypic antibodies; (c) effects on the Fas apoptotic pathway via agonistic and antagonistic anti-Fas autoantibodies; (d) regulation of complement components; (e) modulation of cytokine secretion; (f) hindrance of natural-killer cell activity; (g) inhibition of matrix metalloproteinase-9; (h) suppression of NFkB activation and IkB degradation; (i) G1 cell cycle arrest; (j) prevention of tumor growth; (k) decrease in leukocyte recruitment; (l) attenuation of T-cell stimulation; (m) effects on antibody kinetics; and (n) effects on dendritic cells. The variant mechanisms of IVIg are believed to cooperate in a synergistic way, which all together point to IVIg as a therapeutic preparation with anti-inflammatory, antiself-reactivity, antimetastatic, and embryo-protective effects. This article reviews several main mechanisms of IVIg in order to shed some light on the set of therapeutic effects of IVIg, which are not yet fully understood.

MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomised, double-blind, placebo-controlled, phase 3 study

“…These endpoints immunomodulatory antibodies in human plasma has been documented for some time 27,28,29 . This study 7…”

Management of RSV infections in adult recipients of hematopoietic stem cell transplantation

“…45,46 IVIG and RSV-IVIG have been shown to mediate the respiratory tract inflammation induced by RSV through cytokines; however, the role of chemokines in the action of PVZ requires further elucidation. 39,45,[47][48][49][50][51][52] Combination therapy with ribavirin and IVIG or RSV-IVIG has been shown to reduce pulmonary viral load to a greater degree than ribavirin alone in an animal model of RSV infection 49 and improves clinical outcome when initiated before the need for mechanical ventilation in HSCT patients. 53 …”

Autoimmunity in Neurological and Psychiatric Disorders: Participation of Antibodies and Cytokines in the Immunopathogenesis of these Diseases

“…The possible mechanisms of action are not yet well established, but it is believed that IVIG has immunosuppressive activity on B cells, T cells and antigen presenting cells, downregulation of complement proteins, suppression of NFkB activation and IkB degradation [35][36][37] and actions on the idiotypic-antiidiotypic network [38], enhances the expansion of T regulatory cells [39], neutralizes pathogenic autoantibodies [40,41], remyelinisation, release of cytokines and cytokine antagonists and modulation of cell proliferation and apoptosis [42][43][44]. IVIG was not recommended for 8 conditions including paraproteinemic neuropathy (IgM variant), intractable childhood epilepsy, inclusion body myositis, amyotropic lateral sclerosis, adrenoleukodystrophy, autism, critical illness polyneuropathy and POEMS syndrome characterized by polyneuropathy, organomegaly, endocrinopathy or edema, M-protein and skin abnormalities [45].…”