Intravenous Immunoglobulin and Cytokines

Abstract

The presence of natural autoantibodies against cytokines has been reported in healthy individuals. Because circulating cytokines may be implicated in the clinical outcome of numerous diseases, the mode of action of intravenous immunoglobulin (IVIg) (pooled from sera over a thousand normal individuals) may involve immunomodulation of the cytokine network. We review the anti-cytokine effects of IVIg as well as the consequences of IVIg infusions on cytokine production. Furthermore, IVIg exerts therapeutic effects in autoimmune diseases and lymphoid malignancies. These two conditions have in common an overproduction of BAFF (for B-cell-activating factor of the TNF family). The presence of antibodies with BAFF and APRIL (a proliferation-inducing ligand) specificity was investigated. We found that IVIg recognizes BAFF and APRIL and that IVIg binding prevents BAFF from exerting its antiapoptotic effect on B cells. These anti-BAFF IgGs might prevent the deleterious effects of BAFF in B-cell-mediated autoimmune diseases.

Intravenous immunoglobulin as clinical immune-modulating therapy

“…Intravenous immunoglobulin alters Band T-cell interactions and downregulates pathogenic antibody production. 8 …”

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

“…IVIG may also affect the cellular immune response by altering the interaction of T-cells with antigen presenting cells and by hastening apoptosis of autoreactive T-cells [352]. Additionally, IVIG may interfere with the differentiation, activation, and proliferation of B cells, enhance their apoptosis, and block the activity of cells that release autoantibodies [359][360][361][362]. Additional mechanisms of action for IVIG have also been postulated, but by and large, the mechanism of action of IVIG remains unclear [363][364][365].…”

The place of intravenous immunoglobulin in rheumatic diseases

“…Предполагаемые механизмы действия ВВИГ включа-ют взаимодействие с антиидиотипической сетью, систе-мами комплемента и цитокинов, подавление провоспали-тельных цитокинов, таких как фактор некроза опухоли α (ФНОα), интерлейкин (ИЛ) 1α, ИЛ6, снижение экспрес-сии молекул адгезии [3] и потребления компонентов ком-племента (С3а, С3b, C4b и C5a) [4], увеличение в крови уровня противовоспалительных цитокинов (ИЛ10), цито-лиз клеток-мишеней посредством комплемент-и антите-ло-зависимой клеточно-опосредованной цитотоксично-сти и индукции апоптоза клеток-мишеней через рецепто-ры Fc-фрагмента, а также сиализацию Fc-фрагмента IgG; нейтрализацию патогенных аутоантител и модуляцию мо-лекул активации и костимуляции, влияющих на диффе-ренцировку Т-и В-клеток и дендритных клеток [2,5,6]. ВВИГ подавляет экспансию аутореактивных В-лимфоци-тов через FcgRIIB-сигнальный путь, идиотип-опосредо-ванное ингибирование рецепторов В-клеток и нейтрали-зацию цитокинов, например, таких как фактор активации В-клеток (BAFF и APRIL) [6].…”