Administration of intravenous immunoglobulin (IVIG) in vivo-down-regulatory effects on the IL-1 system

Modulation of the cytokine network may be of importance for the beneficial effects of therapy with IVIG seen in a wide range of immune-mediated disord ers. In the present study we investigate the effect of IVIG administration in vivo on the IL-1 system in 12 patients with primary hypogammaglobulinaem ia. Before IVIG infusion these patients had significantly elevated levels o f IL-1 alpha and IL-1 alpha both in plasma and in supernatants from periphe ral blood mononuclear cells (PBMC) compared with healthy controls. After on e bolus infusion with IVIG (0.4 g/kg) we found a significant change in the profile of the components of the IL-1 system: a marked increase in levels o f IL-1 receptor antagonist (IL-1Ra) and neutralizing antibodies against IL- 1 alpha, a moderate decrease in levels of IL-1 alpha, IL-1 beta and soluble (s) IL-1 receptor type I and a significant increase in sIL-1 receptor type II levels. These changes were found both in plasma and in PBMC isolated af ter IVIG administration. Furthermore, pooled serum obtained after IVIG infu sion suppressed lipopolysaccharide- and staphylococcal enterotoxin B-stimul ated, but not phorbol myristate acetate-stimulated, release of IL-1 alpha a nd IL-1 beta from PBMC isolated from healthy controls. Finally, these chang es in circulating levels of various IL-1 modulators after IVIG infusion app eared to cause a significantly impaired ability of IL-1 to stimulate PBMC f or tumour necrosis factor-alpha release. Our findings suggest that IVIG adm inistration may not only down-regulate the activity in the IL-1 system, but also hamper IL-1 stimulation of PBMC.