Intravenous immunoglobulin preparations induce mild activation of neutrophils in vivo via triggering of macrophages studies in a rat model

Despite widespread use in various immune disorders, the in vivo mechanisms of action of intravenous immunoglobulin (IVIG) preparations are not well kn own. We previously reported that human neutrophils degranulate after incuba tion with IVIG in vitro as a result of interaction with Fc gamma RII. The p urpose of this study was to determine whether IVIG might stimulate neutroph ils in vivo. Anaesthetized rats received a bolus intravenous injection of I VIG preparations, containing either high (aged IVIG) or low (fresh IVIG) am ounts or IgG dimers at a dose of 250 mg/kg. Administration of aged IVIG ind uced neutrophil activation in vivo, whereas no effect was observed after in fusion of fresh IVIG. Histological examination of lung tissue demonstrated mild influx of neutrophils into the pulmonary tissue after aged IVIG admini stration, though gross damage did not occur. Macrophage-depleted rats no lo nger showed activation of neutrophils after infusion of aged IVIG, suggesti ng that neutrophils become activated via an indirect macrophage dependent w ay. We conclude that IVIG induces a mild activation of neutrophils in vivo via triggering of macrophages depending on the amount of IgG dimers. For th is reason, IVIG preparations with a high content of dimers may not always b e as harmless as generally believed and may be responsible for some of the side-effects observed during IVIG infusions.